Libre Pathology - User contributions [en]

User:Sarah A

2020-03-05T19:07:58Z

Sarah A: /* Edits to work on: */

==Edits to work on:==
*Pathology resources
**[[pathology books]]
**online resources
***[[Links]] page
***ExpertPath

*Education etc
**the giving of feedback
***"From Cheerleader to Coach: The Developmental Progression of Bedside Teachers in Giving Feedback to Early Learners"
**study strategies (appropriate for here? Are there things to quote or would this be too close to original research?)
**research in pathology
***quote the paper on doing research in pathology (in my shared drive)
**use of social media (#pathtwitter)
**pathology bioethics

*IHC
**GU IHC pitfalls article

*Pathology history
**History of frozen sections from Biopsy interpretation: the frozen section

Prostate cancer

2020-03-05T15:59:46Z

Sarah A: /* Situations where prostate adenocarcinoma may be missed */

{{ Infobox diagnosis
| Name = Prostate carcinoma
| Image = Prostate cancer with Gleason pattern 4 low mag.jpg
| Width =
| Caption = Prostate carcinoma. [[H&E stain]].
| Micro = major criteria: abnormal architecture (increased gland density, usu. small circular glands, "infiltrative growth" pattern), basal cells lost, cytological abnormalities (nuclear enlargement, nucleoli); minor criteria: nuclear hyperchromasia, wispy blue mucin, pink amorphous secretions, intraluminal crystalloid, amphophilic cytoplasm, adjacent [[HGPIN]], mitoses
| Subtypes =
| LMDDx = [[high-grade prostatic intraepithelial neoplasia]], [[atypical small acinar proliferation]] (biopsy only), [[prostatic atrophy]], [[seminal vesicle]], [[basal cell hyperplasia of the prostate|basal cell hyperplasia]], others
| Stains =
| IHC = PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
| EM =
| Molecular = +/-[[BRCA1]] mutation (genetic predisposition), +/-[[BRCA2]] mutation (genetic predisposition)
| IF =
| Gross = usu. posterior aspect of the prostate - often not apparent at gross
| Grossing = [[prostate biopsy]], [[prostate chips]], [[radical prostatectomy]]
| Staging = [[prostate cancer staging]]
| Site = [[prostate gland]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs = firm, nodular prostate on digital rectal exam
| Symptoms = often asymptomatic
| Prevalence = very common
| Bloodwork = PSA elevated (common)
| Rads = hypoechoic areas, no apparent abnormality
| Endoscopy =
| Prognosis = good-to-poor (depends on [[prostate cancer grading|grade (Gleason score)]] and [[stage]])
| Other =
| ClinDDx = [[prostatitis]], [[nodular hyperplasia of the prostate]]
| Tx = observation (common for low-grade, low tumour burden), radiation or radical prostatectomy
}}
This article deals with '''prostate [[cancer]]'''.

The vast majority of prostate cancers are carcinomas and could be labelled '''prostatic carcinoma'''. Most prostatic carcinomas are gland forming; thus, they can be labelled '''prostatic [[adenocarcinoma]]''' or '''adenocarcinoma of the prostate'''.

Benign pathology of the prostate gland, and prostate histology and anatomy are dealt with in the ''[[prostate gland]]'' article.

=Conventional prostate cancer=
==General==
*Very common.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.<ref>{{cite journal |author=Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD |title=The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients |journal=J. Urol. |volume=150 |issue=2 Pt 1 |pages=379–85 |year=1993 |month=August |pmid=8326560 |doi= |url=}}</ref>{{fact}}
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.

*Risk increased with a [[BRCA1]] or [[BRCA2]] mutation<ref name=pmid23747895>{{Cite journal | last1 = Li | first1 = D. | last2 = Kumaraswamy | first2 = E. | last3 = Harlan-Williams | first3 = LM. | last4 = Jensen | first4 = RA. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Front Biosci (Landmark Ed) | volume = 18 | issue = | pages = 1445-59 | month = | year = 2013 | doi = | PMID = 23747895 }}</ref> - families have a mix of [[breast cancer]] and prostate cancer.
**BRCA2 mutation risk >8x for men over 65 years old.<ref name=pmid22522501>{{Cite journal | last1 = Castro | first1 = E. | last2 = Eeles | first2 = R. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Asian J Androl | volume = 14 | issue = 3 | pages = 409-14 | month = May | year = 2012 | doi = 10.1038/aja.2011.150 | PMID = 22522501 }}</ref>
**A BRCA2 founder mutation is described in French Canadians.<Ref name=pmid23318356>{{Cite journal | last1 = Taherian | first1 = N. | last2 = Hamel | first2 = N. | last3 = Bégin | first3 = LR. | last4 = Bismar | first4 = TA. | last5 = Goldgar | first5 = DE. | last6 = Feng | first6 = BJ. | last7 = Foulkes | first7 = WD. | title = Familial prostate cancer: the damage done and lessons learnt. | journal = Nat Rev Urol | volume = 10 | issue = 2 | pages = 116-22 | month = Feb | year = 2013 | doi = 10.1038/nrurol.2012.257 | PMID = 23318356 }}</ref>

===Management===
====Dirty first approximation====
*The management changes between [[Gleason score]] 6, 7 (3+4), 7 (4+3) and 8.

Typically, the implications are:
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 7 with a bit of Gleason pattern 4 and a low tumour volume: it is reasonable to watch ''or'' do something. ‡
* Gleason 7 with a lot of Gleason pattern 4 ''or'' a high tumour volume: do something -- surgery ''or'' radiation therapy.
* Gleason 8+: bad cancer -- do something quickly!

Note:
* ‡ It has been said that ''Gleason score 7 with a bit of Gleason pattern 4 is the new Gleason score 6''.

Bottom line:
*You want to be sure when you call something Gleason pattern 4.

====Observational strategies====
*Delay of definitive treatment (surgery ''or'' radiation).
*Common in the management of prostate cancer.

Classification:<ref name=pmid23126653>{{Cite journal | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume = | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi = | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
*Active surveillance (AS).
**Low risk of progression.
**May get definitive treatment later.
*Watchful waiting (WW).
**Higher risk of progression.

Note:
*There is no agreed upon set of criteria for active surveillance, and the large number of criteria out there vary significantly.<ref name=pmid22314081>{{Cite journal | last1 = Palisaar | first1 = JR. | last2 = Noldus | first2 = J. | last3 = Löppenberg | first3 = B. | last4 = von Bodman | first4 = C. | last5 = Sommerer | first5 = F. | last6 = Eggert | first6 = T. | title = Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. | journal = BJU Int | volume = 110 | issue = 6 Pt B | pages = E172-81 | month = Sep | year = 2012 | doi = 10.1111/j.1464-410X.2012.10935.x | PMID = 22314081 }}</ref>

=====Active surveillance=====
The ''Klotz'' criteria for active surveillance - pathologic factors only:<ref name=pmid22314081/><ref>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for prostate cancer: for whom? | journal = J Clin Oncol | volume = 23 | issue = 32 | pages = 8165-9 | month = Nov | year = 2005 | doi = 10.1200/JCO.2005.03.3134 | PMID = 16278468 }}</ref>
*Gleason score 6 or less.
*All biopsies cores < 50% involvement.
*One or two cores involved.<ref>URL: [http://www.active-surveillance.com/laurence-klotz-md/ http://www.active-surveillance.com/laurence-klotz-md/]. Accessed on: 12 July 2013.</ref><ref name=pmid23548978>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance: patient selection. | journal = Curr Opin Urol | volume = 23 | issue = 3 | pages = 239-44 | month = May | year = 2013 | doi = 10.1097/MOU.0b013e32835f8f6b | PMID = 23548978 }}</ref><ref name=pmid22891078>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for low-risk prostate cancer. | journal = F1000 Med Rep | volume = 4 | issue = | pages = 16 | month = | year = 2012 | doi = 10.3410/M4-16 | PMID = 22891078 | PMC = 3412317 }}</ref>
Clinical criteria:
*PSA <= 10 ng/mL.<ref name=pmid22314081/>
*Negative DRE.

==Gross==
*Prostate cancer is uncommonly apparent on gross.
*Classic location: posterior aspect of the prostate.

===Radiology===
*Hypoechoic areas = suspicious for cancer.
**It seems that size of the area matters.
***Small hypoechoic areas (<0.2 cm3) have cancer less than 4% of the time.<ref name=pmid9933054>{{Cite journal | last1 = Fleshner | first1 = NE. | last2 = O'Sullivan | first2 = M. | last3 = Premdass | first3 = C. | last4 = Fair | first4 = WR. | title = Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL. | journal = Urology | volume = 53 | issue = 2 | pages = 356-8 | month = Feb | year = 1999 | doi = | PMID = 9933054 }}</ref>
***One study suggests hypoechoic lesions tend to have a worse outcome;<ref name=pmid22920545>{{Cite journal | last1 = Nakano Junqueira | first1 = VC. | last2 = Zogbi | first2 = O. | last3 = Cologna | first3 = A. | last4 = Dos Reis | first4 = RB. | last5 = Tucci | first5 = S. | last6 = Reis | first6 = LO. | last7 = Westphalen | first7 = AC. | last8 = Muglia | first8 = VF. | title = Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? | journal = Ultrasound Med Biol | volume = 38 | issue = 10 | pages = 1689-94 | month = Oct | year = 2012 | doi = 10.1016/j.ultrasmedbio.2012.06.006 | PMID = 22920545 }}</ref> however, this is not supported by an older study.<ref name=pmid1688955>{{Cite journal | last1 = Devonec | first1 = M. | last2 = Fendler | first2 = JP. | last3 = Monsallier | first3 = M. | last4 = Mouriquand | first4 = P. | last5 = Maquet | first5 = JH. | last6 = Mestas | first6 = JL. | last7 = Dutrieux-Berger | first7 = N. | last8 = Perrin | first8 = P. | title = The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. | journal = J Urol | volume = 143 | issue = 2 | pages = 316-9 | month = Feb | year = 1990 | doi = | PMID = 1688955 }}</ref>

===Prostatectomy grossing===
{{Main|Radical prostatectomy}}

===Cytoprostatectomy grossing===
{{Main|Cystoprostatectomy grossing}}
*Limited sampling of the prostate may lead to undersampling error.<ref name=pmid11182038>{{Cite journal | last1 = Cindolo | first1 = L. | last2 = Benincasa | first2 = G. | last3 = Autorino | first3 = R. | last4 = Domizio | first4 = S. | last5 = De Rosa | first5 = G. | last6 = Testa | first6 = G. | last7 = D'Armiento | first7 = M. | last8 = Altieri | first8 = V. | title = Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study. | journal = Oncol Rep | volume = 8 | issue = 2 | pages = 269-71 | month = | year = | doi = | PMID = 11182038 }}</ref>

==Microscopic==
===Criteria as a list===
Major criteria (the ABCs of prostate pathology):<ref name=pmid17213347>{{cite journal |author=Humphrey PA |title=Diagnosis of adenocarcinoma in prostate needle biopsy tissue |journal=J. Clin. Pathol. |volume=60 |issue=1 |pages=35–42 |year=2007 |month=January |pmid=17213347 |pmc=1860598 |doi=10.1136/jcp.2005.036442 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed}}</ref>
#Architecture.
#*Increased gland density.
#*Small circular glands.
#**In rare subtypes - large branching glands.
#*"Infiltrative growth" pattern - malignant glands between benign ones.
#**Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f1.html#figure-title Infiltrative growth pattern (nature.com)].
#Basal cells lacking.
#Cytological abnormalities:
#*Nuclear enlargement (subtle).
#*[[Nucleoli]] (prominent).

Minor criteria:<ref name=pmid17213347/>
#Nuclear hyperchromasia.
#Wispy blue mucin.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f3.html#figure-title Wispy blue mucin (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Pink amorphous secretions.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html Pink amorphous secretions (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Intraluminal crystalloid.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f4.html#figure-title Intraluminal crystalloid (nature.com)] - from Epstein.<ref name=pmid14739905/>
#Amphophilic cytoplasm.
#*Amphopilic is said to be ''bluish-red''<ref>URL: [http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref> -- though might also be described as ''blue-grey''.
#**Image: [http://www.webpathology.com/image.asp?n=4&Case=20 Amphophilic cytoplasm is prostate carcinoma].
#Adjacent [[HGPIN]].
#Mitoses - quite rare.

Extent/quantity criteria:
*There is no agreed upon minimum number of glands; however, one paper suggests that agreement among experts is low with 5 or less glands.<ref name=pmid20061936>{{Cite journal | last1 = Van der Kwast | first1 = TH. | last2 = Evans | first2 = A. | last3 = Lockwood | first3 = G. | last4 = Tkachuk | first4 = D. | last5 = Bostwick | first5 = DG. | last6 = Epstein | first6 = JI. | last7 = Humphrey | first7 = PA. | last8 = Montironi | first8 = R. | last9 = Van Leenders | first9 = GJ. | title = Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 169-77 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c7997b | PMID = 20061936 }}</ref>
**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>

Features considered pathognomonic for prostate carcinoma by some authorities:<ref name=pmid16613324>{{Cite journal | last1 = Egevad | first1 = L. | last2 = Allsbrook | first2 = WC. | last3 = Epstein | first3 = JI. | title = Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists. | journal = Hum Pathol | volume = 37 | issue = 3 | pages = 292-7 | month = Mar | year = 2006 | doi = | PMID = 16613324 }}</ref><ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref>
#Perineural invasion.
#*Must be circumferential (>95% of circumference{{fact}}).
#Glomeruloid bodies.
#[[Collagenous micronodules]] also known as ''mucinous fibroplasia''.

<gallery>
Image: Intraluminal eosinophilic crystalloid of prostate gland - high mag.jpg| Intraluminal eosinophilic crystalloid - high mag. (WC)
Image: Prostate carcinoma with blue mucin -- very high mag.jpg | Whispy blue mucin - very high mag. (WC)
Image: Prostate carcinoma with blue mucin - a1 -- intermed mag.jpg | Whispy blue mucin - intermed. mag. (WC)
</gallery>

===Divided into high and low power===
====Low power features====
*Architecture is the '''key''' to diagnosing low grade cancer.
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Sharp transition between gland border and lumen.
***Loss of epithelial folding at the epithelium-gland lumen interface - "punched-out" appearance.
**Eosinophilic debris within the gland lumen (pink amorphous secretions, intraluminal crystalloid).
**Blue-tinged acellular material within the gland lumen (mucin) -- uncommon.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.

====High power features====
*Nuclear changes.
**Hyperchromatic nuclei (like in HGPIN).
**Nuclear enlargement, mild (10%?).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult/impossible to see at low power.
*"Large" nucleoli.
**Visible on intermediate and high power (100x / 200x magnification).
***May be difficult to see - especially if light intensity is low or the staining is of poor quality.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk over-calling something benign).
**"Large" is rarely precisely quantified; 3 micrometres has been suggested as "large" based on one study.<ref name=pmid1688728>{{Cite journal | last1 = Kelemen | first1 = PR. | last2 = Buschmann | first2 = RJ. | last3 = Weisz-Carrington | first3 = P. | title = Nucleolar prominence as a diagnostic variable in prostatic carcinoma. | journal = Cancer | volume = 65 | issue = 4 | pages = 1017-20 | month = Feb | year = 1990 | doi = | PMID = 1688728 }}</ref>
***Three micrometres is a little more than 1/3 of [[RBC]] diameter.
*Loss of basal cells - diagnostic feature.
**Like in [[breast pathology]] (where one looks for loss of myoepithelial cells) - this may be difficult to see.

Notes:
*Mitoses are not a common feature.
**If you find them the lesion is probably high-grade.
**Generally, it isn't worth looking for them.

===Mimics===
Mimics of prostate adenocarcinoma:<ref>{{Ref TPoSP|100-3}}</ref>
{| class="wikitable sortable"
! Entity
! Key feature
! Detailed microscopic
! Other
! Image
|-
| Adenosis ([[AKA]] ''atypical adenomatous hyperplasia'')
| gradual transition between normal & small gland (NOT two populations)
| many small glands, lack nuclear size variation, basal layer present
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| [[Image:Adenosis of prostate_--_intermed_mag.jpg|thumb|150px|center| Adenosis of prostate. (WC)]]
|-
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| analogous to [[sclerosing adenosis of the breast]]{{fact}}
| [http://webpathology.com/image.asp?case=21&n=40 Sclerosing adenosis (webpathology.com)]
|-
| [[atrophy of the prostate|Atrophy]]
| sharp angulation of gland
| nuclear hyperchromasia, scant cytoplasm
| may appear right beside non-atrophic tissue
| [[Image:Atrophic_prostatic_glands_--_high_mag.jpg|thumb|150px|center| Prostatic atrophy. (WC)]]
|-
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
| two distinct cell populations (in epithelial component)
| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| [[Image:Basal_cell_hyperplasia_of_prostate_-_high_mag.jpg|thumb|150px|center| Prostatic BCH. (WC)]]
|-
| [[Bulbourethral gland]]
| no nuclear atypia
| clear cytoplasm
| apex of prostate
| [[Image:Bulbourethral gland -- very high mag.jpg |thumb|150px|center| Bulbourethral gland. (WC)]]
|-
| [[Seminal vesicles]] / ejaculatory ducts
| lipofuscin (yellow granular material in cytoplasm), smudge cells (smeared appearance + hyperchromatic)
| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| [[Image:Seminal_vesicle_high_mag.jpg |thumb|150px|center|Seminal vesicles. (WC)]]
|-
| [[Radiation effect]]
| marked nuclear size variation
| increased stroma (fibrosis), lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of [[postradiation prostatic carcinoma|postradiation cancer]]
| [[Image:Prostate_with_radiation_changes_--_high_mag.jpg|thumb|150px|center|Radiation change. (WC)]]
|-
| Prostatitis
| inflammatory cells (lymphocytes, plasma cells, PMNs)
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| [[Image:Inflammation_of_prostate.jpg|thumb|150px|center| Prostatic inflammation. (WC)]]
|-
| [[Vasitis nodosa]]
| sperm within ducts, clinical history (usu. post-[[vasectomy]])
| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| [[Image:Vasitis nodosa -11- intermed mag.jpg|thumb|150px|center| VN. (WC)]]
|}
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.

===Situations where prostate adenocarcinoma may be missed===
Key reasons for false negative prostate samples<ref>{{cite journal |vauthors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}}</ref>:
*Tissue artefacts (try levels and/or IHC):
**Crush artefact
**Thick sections
**Aberrant H&E staining
**Freezing artefact
**Cautery
*Minimal adenocarcinoma (less than 1mm long or involving less than 5% of a core biopsy):
*Prostatic adenocarcinoma variants that mimic benign:
**[[Atrophic prostate carcinoma]]
**[[Pseudohyperplastic adenocarcinoma]]
**[[Foamy gland adenocarcinoma]]
**[[PIN-like adenocarcinoma]]
**Microcystic adenocarcinoma
*Single cells of Gleason 5 adenocarcinoma (missed or mistaken for lymphocytes; try IHC for cytokeratins, prostatic and/or hematologic markers)
*Treatment effect (check clinical information and look for treatment effect in benign glands)

===Prostate cancer grading===
{{Main|Prostate cancer grading}}
It covers the ''Gleason grading system'' and the (new) ''prognostic grade groupings''.

===Staging parameters, margins and more===
====Surgical margins====
{{Main|Surgical margins}}
*Positive is ''tumour touching [[ink]]''.† <ref name=pmid22578729>{{Cite journal | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
**"Close" margins (<0.1 mm) have an increased recurrence risk.<ref name=pmid22578729/>

Notes:
*Surgical margin - where the surgeon cut.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
* † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.<ref>URL: [http://urology.jhu.edu/newsletter/prostate_cancer410.php http://urology.jhu.edu/newsletter/prostate_cancer410.php]. Accessed on: 26 March 2013.</ref>

=====Rates and implication=====
Positivity rate varies substantially (13-44%):
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*France: 13-17% -- PSA and prostate size predictors of positivity.<ref name=pmid22860572>{{Cite journal | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>

Note:
*Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.<ref name=pmid22860630/>

The impact of positive margins:
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Bladder neck margin positivity may change the T-stage - see below.

=====Bladder neck margin=====
{{Main|Bladder neck invasion}}
:[[AKA]] ''invasion of the bladder neck''.<ref name=pmid19914651/>
*Bladder neck margin positivity typically is '''pT3a'''.<ref name=pmid23225909>{{Cite journal | last1 = Chung | first1 = MS. | last2 = Lee | first2 = SH. | last3 = Lee | first3 = DH. | last4 = Chung | first4 = BH. | title = Evaluation of the 7th American Joint Committee on cancer TNM staging system for prostate cancer in point of classification of bladder neck invasion. | journal = Jpn J Clin Oncol | volume = 43 | issue = 2 | pages = 184-8 | month = Feb | year = 2013 | doi = 10.1093/jjco/hys196 | PMID = 23225909 }}</ref>
*Seen in approximately 1% of prostatectomies.<ref name=pmid19914651>{{Cite journal | last1 = Pierorazio | first1 = PM. | last2 = Epstein | first2 = JI. | last3 = Humphreys | first3 = E. | last4 = Han | first4 = M. | last5 = Walsh | first5 = PC. | last6 = Partin | first6 = AW. | title = The significance of a positive bladder neck margin after radical prostatectomy: the American Joint Committee on Cancer Pathological Stage T4 designation is not warranted. | journal = J Urol | volume = 183 | issue = 1 | pages = 151-7 | month = Jan | year = 2010 | doi = 10.1016/j.juro.2009.08.138 | PMID = 19914651 }}</ref>

====Extraprostatic extension====
:Abbreviated ''EPE''.
{{Main|Prostate cancer staging#Extraprostatic extension}}

====Seminal vesicle invasion====
:Abbreviated ''SVI''.
{{Main|Prostate cancer staging#Seminal vesicle invasion}}

====Perineural invasion====
{{Main|Perineural invasion}}
*''Not'' a staging parameter.
*Seen in approximately 20% of core biopsies.<ref name=pmid16096404>{{Cite journal | last1 = Ali | first1 = TZ. | last2 = Epstein | first2 = JI. | title = Perineural involvement by benign prostatic glands on needle biopsy. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1159-63 | month = Sep | year = 2005 | doi = | PMID = 16096404 }}</ref>
*Complete wrapping of a nerve by epithelium is considered pathognomonic for cancer.<ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref><ref name=pmid16096404/>

Note:
*Occasionally, benign glands are found perineural.<ref name=pmid16096404/>
**These should ''not'' completely wrap around the nerve and should be cytologically benign.

==IHC==
===General recommendations===
ISUP consensus statement:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*Should ''not'' be used if cancer is obvious.
*Should ''not'' be used if it isn't going change the clinical management.

===Prostate markers===
*[[PSA]] (prostate specific antigen) +ve.
*[[PSAP]] (prostatic specific acid phosphatase) +ve. †
*P501S +ve. ‡
*[[NKX3.1]] +ve. ‡

Notes:
*† PSAP may be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref>
*‡ P501S and NKX3.1 are considered second line markers.<ref name=pmid25025364/>
*Prostate carcinoma is typically CK7 -ve and CK20 -ve; however, in high [[Gleason score]] cancers focal positivity of these markers can be seen.<ref name=pmid11888088>{{Cite journal | last1 = Goldstein | first1 = NS. | title = Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. | journal = Am J Clin Pathol | volume = 117 | issue = 3 | pages = 471-7 | month = Mar | year = 2002 | doi = 10.1309/G6PR-Y774-X738-FG2K | PMID = 11888088 }}</ref>
**CK7: >25-50% staining seen in ~5% of cases.
***>50% staining with CK7 is not report.
**CK20: >25-50% staining seen in ~10% of cases.
***>50% staining with CK20 is not reported.

===Benign prostate versus neoplastic prostate===
*AMACR +ve.
*p63 -ve.
*HMWCK (34betaE12) -ve.

Combination immunostains:
*''PIN-4'' -- consists of: CK5 + CK14 + p63 + P504S (AMACR).<ref>URL: [http://biocare.net/wp-content/uploads/225DS.pdf http://biocare.net/wp-content/uploads/225DS.pdf]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/ http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.webpathology.com/image.asp?case=96&n=5 http://www.webpathology.com/image.asp?case=96&n=5]. Accessed on: 18 October 2011.</ref>
**[[AKA]] ''PIN''.
**[[AKA]] ''CAP''.
***Why '''CAP'''?
****A. '''CA'''ncer of the '''P'''rostate.

Other IHC stains:
*AR +ve -- in prostate confined cancer.
**Usually -ve in lymph node +ve disease.<ref name=pmid20878946>{{Cite journal | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>

Note:
*Bcl-2 marks basal cells in prostate cancer.<ref name=pmid20189848>{{Cite journal | last1 = Boran | first1 = C. | last2 = Kandirali | first2 = E. | last3 = Yilmaz | first3 = F. | last4 = Serin | first4 = E. | last5 = Akyol | first5 = M. | title = Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma. | journal = Urol Oncol | volume = 29 | issue = 6 | pages = 614-23 | month = | year = | doi = 10.1016/j.urolonc.2009.11.013 | PMID = 20189848 }}</ref>

====Prostate carcinoma versus urothelial carcinoma====
The ISUP panel recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*PSA +ve (-ve in UCC).
*GATA3 -ve (+ve in UCC).

Another panel - if GATA3 isn't available:
*Prostate: PSA +ve, p63 -ve, HWMCK -ve.
*Urothelial: p63 +ve, HWMCK +ve, PSA -ve.

Notes:
*AMACR not useful; it is positive in ~50% of [[UCC]].<ref name=pmid16315020>{{Cite journal | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*CK7 and CK20 are typically negative in prostate carcinoma, and classically positive in urothelial carcinoma.
*CK34betaE12 may be positive in prostate cancer; 43% of cases in one small series of cases with lymph node metastases.<ref name=pmid9024071>{{Cite journal | last1 = Googe | first1 = PB. | last2 = McGinley | first2 = KM. | last3 = Fitzgibbon | first3 = JF. | title = Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma. | journal = Am J Clin Pathol | volume = 107 | issue = 2 | pages = 219-23 | month = Feb | year = 1997 | doi = | PMID = 9024071 }}</ref>

===Rate of utilization===
*Dependent on practise setting.
**One tertiary academic institution uses it on ~ 40% of cases.<ref>{{Cite journal | last1 = Watson | first1 = K. | last2 = Wang | first2 = C. | last3 = Yilmaz | first3 = A. | last4 = Bismar | first4 = TA. | last5 = Trpkov | first5 = K. | title = Use of immunohistochemistry in routine workup of prostate needle biopsies: a tertiary academic institution experience. | journal = Arch Pathol Lab Med | volume = 137 | issue = 4 | pages = 541-5 | month = Apr | year = 2013 | doi = 10.5858/arpa.2012-0145-OA | PMID = 23273390 }}</ref>

==Molecular changes in prostate cancer==
A fusion gene between ''TMPRSS2'' and ''ERG'' is described.<ref name=pmid20478527>{{cite journal | author = Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM | title = An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression | journal = Cancer Cell | volume = 17 | issue = 5 | pages = 443–54 | year = 2010 | month = May | pmid = 20478527 | pmc = 2874722 | doi = 10.1016/j.ccr.2010.03.018 | url = }}</ref><ref name=omim602060>{{OMIM|602060}}</ref>
*Both genes are on chromosome 21.
*Currently ''not'' used diagnostically.
*Fusion gene seen in approximately 50% of prostate cancer.<ref name=omim602060>{{OMIM|602060}}</ref>
*A subset of ''TMPRSS2-ERG'' known as ''2+Edel'' (seen in ~7% of all prostate cancer cases) predicts poor survival.<ref name=pmid17637754>{{Cite journal | last1 = Attard | first1 = G. | last2 = Clark | first2 = J. | last3 = Ambroisine | first3 = L. | last4 = Fisher | first4 = G. | last5 = Kovacs | first5 = G. | last6 = Flohr | first6 = P. | last7 = Berney | first7 = D. | last8 = Foster | first8 = CS. | last9 = Fletcher | first9 = A. | title = Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. | journal = Oncogene | volume = 27 | issue = 3 | pages = 253-63 | month = Jan | year = 2008 | doi = 10.1038/sj.onc.1210640 | PMID = 17637754 }}</ref>

==Sign out==
===Prostatectomy specimens===
*A prostatectomy that appears to be negative should be worked-up. This is discuss in the ''[[negative prostatectomy]]'' article.
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP checklist].

<pre>
A. LYMPH NODES, RIGHT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

B. LYMPH NODES, LEFT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

C. PROSTATE GLAND AND SEMINAL VESICLES, RADICAL PROSTATECTOMY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4), pT2c pN0.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>

===Transurethral resection of prostate===
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 6/10 (3+3);
-- Approximately 2% of tissue involved;
-- Please see tumour summary.

Comment:
The World Health Organization (WHO) grade is: 1 out of 5.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 7/10 (3+4);
-- Approximately 4% of tissue involved;
-- Please see tumour summary.
- Benign inflamed urothelium.

Comment:
The World Health Organization (WHO) grade is: 2 out of 5. Gleason pattern 3 represents 90% of the tumour, and Gleason pattern 4 represents 10% of the tumour.
</pre>

====Block letters====
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.

TUMOUR SUMMARY - TRANSURETHRAL RESECTION OF PROSTATE (TURP).

PROCEDURE: TRANSURETHRAL PROSTATIC RESECTION.
SPECIMEN SIZE: WEIGHT: 10 GRAMS.
HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).

HISTOLOGIC GRADING:
PRIMARY PATTERN: 3.
SECONDARY PATTERN: 4 (40% OF TUMOUR).
TOTAL GLEASON SCORE: 7 (3+4).

TUMOUR QUANTITATION - PERCENTAGE OF PROSTATIC TISSUE INVOLVED BY TUMOUR: 80 %.

PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
SEMINAL VESICLE INVASION: NOT IDENTIFIED.
LYMPH-VASCULAR INVASION: NOT IDENTIFIED.
PERINEURAL INVASION: NOT IDENTIFIED.

ADDITIONAL PATHOLOGIC FINDINGS:
HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).
NODULAR PROSTATIC HYPERPLASIA.
CHRONIC INFLAMMATION.
</pre>

<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- Adenocarcinoma, Gleason score 7 (3+4)
- Approximately 3% of sampled tissue involved
- Please see tumour summary

Tumour summary:
Procedure: Transurethral resection of prostate
Specimen weight: 11.7 g
Histologic type: Adenocarcinoma, acinar type

Histologic grade:
Primary pattern: 3
Secondary pattern: 4 (<15% of tumor)
Total Gleason score: 7/10 (3+4)

Tumor volume: 3% of tissue

Periprostate fat invasion: Periprostatic fat not identified
Seminal vesicle invasion: Seminal vesicle not identified
Lymphovascular inasion: Not identified
Perineural invasion: Not identified

Additional findings:
Glandular and stromal hyperplasia
Mild chronic inflammation
</pre>

===Biopsy specimens===
Important elements - a list:<ref name=pmid17213347/>
#Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
#Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
#Number of cores and number involved, e.g. "2/3 cores involved by cancer".
#Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour". ‡
#Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
#Presence of [[perineural invasion]].
#Presence of extension into fat (extraprostatic extension).

Notes:
*‡ "Percent area involved" may seem like an odd thing to request 'cause it is sampling dependent, i.e. if the radiologist sticks the biopsy needle deeper into the lesion more of the core is positive, but urologists think it is important -- more important than perineural invasion.<ref name=pmid15223967>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.<ref name=pmid22688447>{{Cite journal | last1 = Fu | first1 = Q. | last2 = Moul | first2 = JW. | last3 = Bañez | first3 = LL. | last4 = Sun | first4 = L. | last5 = Mouraviev | first5 = V. | last6 = Xie | first6 = D. | last7 = Polascik | first7 = TJ. | title = Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer. | journal = Med Oncol | volume = 29 | issue = 5 | pages = 3339-44 | month = Dec | year = 2012 | doi = 10.1007/s12032-012-0270-4 | PMID = 22688447 }}</ref>

====Completely negative====
<pre>
A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

C. PROSTATE, RIGHT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

D. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

E. PROSTATE, RIGHT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

I. PROSTATE, LEFT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

J. PROSTATE, LEFT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

K. PROSTATE, LEFT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
</pre>

====Negative biopsy in surveillance====
<pre>
COMMENT:
The previous results are noted. The absence of cancer in this biopsy may
be due to sampling.
</pre>

====No glands====
<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN FIBROMUSCULAR TISSUE;
- NO PROSTATIC GLANDULAR TISSUE PRESENT.
</pre>

====Inflammation====
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- ACUTE AND CHRONIC INFLAMMATION.
</pre>

====Positive====
<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 25% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

=====Tumour summaries=====
*These are not completely without controversy.
*It should be noted that treatment is driven by the highest Gleason score.{{fact}}

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- TOTAL GLEASON SCORE: 7.
- PRIMARY PATTERN: 4.
- SECONDARY PATTERN: 3.
- PERCENT OF TUMOUR WITH PATTERN HIGHER THAN GRADE 3: 75%.

- NUMBER OF CORES POSITIVE: 10.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 152 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 44%.

- PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: SEMINAL VESICLE NOT IDENTIFIED.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- PERINEURAL INVASION: PRESENT.

- ADDITIONAL FINDINGS: HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA, CHRONIC INFLAMMATION (FOCAL).
</pre>

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- HIGHEST GLEASON SCORE: 8 (4+4).
- SUMMARY GLEASON SCORE: 7 (4+3).
- PERCENT OF TUMOUR WITH PATTERN 4: 55%.
- PERCENT OF TUMOUR WITH PATTERN 5: 0%.

- NUMBER OF CORES POSITIVE: 12.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 178 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 80%.

- PERINEURAL INVASION: PRESENT.
- PERIPROSTATIC FAT INVASION: PRESENT.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: NOT IDENTIFIED.
</pre>

===Seminal vesicle/ejaculatory duct invasion on biopsy===
<pre>
COMMENT:
The seminal vesicles and ejaculatory ducts have the same histology; thus, it is not
usually possible to confidently differentiate them in a needle biopsy.

SV/ED invasion was demonstrated with CK7, CK34betaE12/AMACR, PSA and p63 immunostaining.
The tumour is PSA and AMACR positive.
</pre>

=Intraductal spread of prostate cancer=
==Intraductal carcinoma of the prostate==
*[[AKA]] ''[[intraductal carcinoma]]''.
*[[AKA]] ''intraductal prostate carcinoma''.
{{Main|Intraductal carcinoma of the prostate}}

=Unusual forms of prostate cancer=
==Prostatic ductal adenocarcinoma==
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
{{Main|Ductal adenocarcinoma of the prostate gland}}

==PIN-like prostatic ductal adenocarcinoma==
{{Main|High-grade prostatic intraepithelial neoplasia-like ductal adenocarcinoma of the prostate}}

==Foamy gland carcinoma==
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862>{{Cite journal | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
{{Main|Foamy gland carcinoma}}

==Atrophic prostate carcinoma==
*[[AKA]] ''atrophic carcinoma''.
{{Main|Atrophic prostate carcinoma}}

==Mucinous prostate carcinoma==
{{Main|Mucinous adenocarcinoma of the prostate}}

==Pseudohyperplastic prostatic adenocarcinoma==
*[[AKA]] ''pseudohyperplastic adenocarcinoma''.
{{Main|Pseudohyperplastic prostatic adenocarcinoma}}

==Prostatic signet ring cell carcinoma==
{{Main|Signet ring cell carcinoma}}
===General===
*Very rare - 9 cases in a series of 29,783 prostate cancer cases.<ref name=pmid21123640>{{Cite journal | last1 = Warner | first1 = JN. | last2 = Nakamura | first2 = LY. | last3 = Pacelli | first3 = A. | last4 = Humphreys | first4 = MR. | last5 = Castle | first5 = EP. | title = Primary signet ring cell carcinoma of the prostate. | journal = Mayo Clin Proc | volume = 85 | issue = 12 | pages = 1130-6 | month = Dec | year = 2010 | doi = 10.4065/mcp.2010.0463 | PMID = 21123640 }}</ref>
*Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.<ref name=pmid21123640/>

===Microscopic===
Features:
*Signet ring cells - see ''[[basics]]'' article.

DDx:
*Acinar adenocarcinoma - Gleason pattern 4 with very small glands.

====Images====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRCC (nih.gov)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f7.html#figure-title Prostatic SRCC (nature.com)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f8.html Prostatic SRCC (nature.com)].
*[http://www.webpathology.com/image.asp?case=23&n=34 Prostatic SRCC (webpathology.com)] - looks like ''acinar adenocarcinoma''.

===Stains===
*Alcian blue-PAS stain +ve.
*[[PAS stain|PAS]] -- 50% of cases +ve.<ref name=pmid21123640/>
*[[Alcian blue stain|Alcian blue]] -- 44% of cases +ve.<ref name=pmid21123640/>

==Sarcomatoid carcinoma of the prostate==
{{Main|Sarcomatoid carcinoma of the prostate}}

==Small cell carcinoma of the prostate gland==
{{Main|Small cell carcinoma of the prostate gland}}

==Adenoid cystic/basal cell carcinoma of the prostate==
*Abbreviated ''ACBCC''.
{{Main|Adenoid cystic/basal cell carcinoma of the prostate}}

==Postradiation prostate cancer==
{{Main|Postradiation prostate cancer}}

=Metastatic disease and other cancers of the prostate=
==Urothelial carcinoma==
{{Main|Urothelial carcinoma of the urethra}}

=See also=
*[[Prostate gland]].
*[[Genitourinary pathology]]

=References=
{{Reflist|2}}

[[Category:Genitourinary pathology]]
[[Category:Prostate carcinoma]]

Prostate cancer

2020-03-05T15:59:09Z

Sarah A: /* Situations where prostate adenocarcinoma may be missed{{cite journal |vauthors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}} */

{{ Infobox diagnosis
| Name = Prostate carcinoma
| Image = Prostate cancer with Gleason pattern 4 low mag.jpg
| Width =
| Caption = Prostate carcinoma. [[H&E stain]].
| Micro = major criteria: abnormal architecture (increased gland density, usu. small circular glands, "infiltrative growth" pattern), basal cells lost, cytological abnormalities (nuclear enlargement, nucleoli); minor criteria: nuclear hyperchromasia, wispy blue mucin, pink amorphous secretions, intraluminal crystalloid, amphophilic cytoplasm, adjacent [[HGPIN]], mitoses
| Subtypes =
| LMDDx = [[high-grade prostatic intraepithelial neoplasia]], [[atypical small acinar proliferation]] (biopsy only), [[prostatic atrophy]], [[seminal vesicle]], [[basal cell hyperplasia of the prostate|basal cell hyperplasia]], others
| Stains =
| IHC = PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
| EM =
| Molecular = +/-[[BRCA1]] mutation (genetic predisposition), +/-[[BRCA2]] mutation (genetic predisposition)
| IF =
| Gross = usu. posterior aspect of the prostate - often not apparent at gross
| Grossing = [[prostate biopsy]], [[prostate chips]], [[radical prostatectomy]]
| Staging = [[prostate cancer staging]]
| Site = [[prostate gland]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs = firm, nodular prostate on digital rectal exam
| Symptoms = often asymptomatic
| Prevalence = very common
| Bloodwork = PSA elevated (common)
| Rads = hypoechoic areas, no apparent abnormality
| Endoscopy =
| Prognosis = good-to-poor (depends on [[prostate cancer grading|grade (Gleason score)]] and [[stage]])
| Other =
| ClinDDx = [[prostatitis]], [[nodular hyperplasia of the prostate]]
| Tx = observation (common for low-grade, low tumour burden), radiation or radical prostatectomy
}}
This article deals with '''prostate [[cancer]]'''.

The vast majority of prostate cancers are carcinomas and could be labelled '''prostatic carcinoma'''. Most prostatic carcinomas are gland forming; thus, they can be labelled '''prostatic [[adenocarcinoma]]''' or '''adenocarcinoma of the prostate'''.

Benign pathology of the prostate gland, and prostate histology and anatomy are dealt with in the ''[[prostate gland]]'' article.

=Conventional prostate cancer=
==General==
*Very common.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.<ref>{{cite journal |author=Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD |title=The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients |journal=J. Urol. |volume=150 |issue=2 Pt 1 |pages=379–85 |year=1993 |month=August |pmid=8326560 |doi= |url=}}</ref>{{fact}}
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.

*Risk increased with a [[BRCA1]] or [[BRCA2]] mutation<ref name=pmid23747895>{{Cite journal | last1 = Li | first1 = D. | last2 = Kumaraswamy | first2 = E. | last3 = Harlan-Williams | first3 = LM. | last4 = Jensen | first4 = RA. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Front Biosci (Landmark Ed) | volume = 18 | issue = | pages = 1445-59 | month = | year = 2013 | doi = | PMID = 23747895 }}</ref> - families have a mix of [[breast cancer]] and prostate cancer.
**BRCA2 mutation risk >8x for men over 65 years old.<ref name=pmid22522501>{{Cite journal | last1 = Castro | first1 = E. | last2 = Eeles | first2 = R. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Asian J Androl | volume = 14 | issue = 3 | pages = 409-14 | month = May | year = 2012 | doi = 10.1038/aja.2011.150 | PMID = 22522501 }}</ref>
**A BRCA2 founder mutation is described in French Canadians.<Ref name=pmid23318356>{{Cite journal | last1 = Taherian | first1 = N. | last2 = Hamel | first2 = N. | last3 = Bégin | first3 = LR. | last4 = Bismar | first4 = TA. | last5 = Goldgar | first5 = DE. | last6 = Feng | first6 = BJ. | last7 = Foulkes | first7 = WD. | title = Familial prostate cancer: the damage done and lessons learnt. | journal = Nat Rev Urol | volume = 10 | issue = 2 | pages = 116-22 | month = Feb | year = 2013 | doi = 10.1038/nrurol.2012.257 | PMID = 23318356 }}</ref>

===Management===
====Dirty first approximation====
*The management changes between [[Gleason score]] 6, 7 (3+4), 7 (4+3) and 8.

Typically, the implications are:
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 7 with a bit of Gleason pattern 4 and a low tumour volume: it is reasonable to watch ''or'' do something. ‡
* Gleason 7 with a lot of Gleason pattern 4 ''or'' a high tumour volume: do something -- surgery ''or'' radiation therapy.
* Gleason 8+: bad cancer -- do something quickly!

Note:
* ‡ It has been said that ''Gleason score 7 with a bit of Gleason pattern 4 is the new Gleason score 6''.

Bottom line:
*You want to be sure when you call something Gleason pattern 4.

====Observational strategies====
*Delay of definitive treatment (surgery ''or'' radiation).
*Common in the management of prostate cancer.

Classification:<ref name=pmid23126653>{{Cite journal | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume = | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi = | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
*Active surveillance (AS).
**Low risk of progression.
**May get definitive treatment later.
*Watchful waiting (WW).
**Higher risk of progression.

Note:
*There is no agreed upon set of criteria for active surveillance, and the large number of criteria out there vary significantly.<ref name=pmid22314081>{{Cite journal | last1 = Palisaar | first1 = JR. | last2 = Noldus | first2 = J. | last3 = Löppenberg | first3 = B. | last4 = von Bodman | first4 = C. | last5 = Sommerer | first5 = F. | last6 = Eggert | first6 = T. | title = Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. | journal = BJU Int | volume = 110 | issue = 6 Pt B | pages = E172-81 | month = Sep | year = 2012 | doi = 10.1111/j.1464-410X.2012.10935.x | PMID = 22314081 }}</ref>

=====Active surveillance=====
The ''Klotz'' criteria for active surveillance - pathologic factors only:<ref name=pmid22314081/><ref>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for prostate cancer: for whom? | journal = J Clin Oncol | volume = 23 | issue = 32 | pages = 8165-9 | month = Nov | year = 2005 | doi = 10.1200/JCO.2005.03.3134 | PMID = 16278468 }}</ref>
*Gleason score 6 or less.
*All biopsies cores < 50% involvement.
*One or two cores involved.<ref>URL: [http://www.active-surveillance.com/laurence-klotz-md/ http://www.active-surveillance.com/laurence-klotz-md/]. Accessed on: 12 July 2013.</ref><ref name=pmid23548978>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance: patient selection. | journal = Curr Opin Urol | volume = 23 | issue = 3 | pages = 239-44 | month = May | year = 2013 | doi = 10.1097/MOU.0b013e32835f8f6b | PMID = 23548978 }}</ref><ref name=pmid22891078>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for low-risk prostate cancer. | journal = F1000 Med Rep | volume = 4 | issue = | pages = 16 | month = | year = 2012 | doi = 10.3410/M4-16 | PMID = 22891078 | PMC = 3412317 }}</ref>
Clinical criteria:
*PSA <= 10 ng/mL.<ref name=pmid22314081/>
*Negative DRE.

==Gross==
*Prostate cancer is uncommonly apparent on gross.
*Classic location: posterior aspect of the prostate.

===Radiology===
*Hypoechoic areas = suspicious for cancer.
**It seems that size of the area matters.
***Small hypoechoic areas (<0.2 cm3) have cancer less than 4% of the time.<ref name=pmid9933054>{{Cite journal | last1 = Fleshner | first1 = NE. | last2 = O'Sullivan | first2 = M. | last3 = Premdass | first3 = C. | last4 = Fair | first4 = WR. | title = Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL. | journal = Urology | volume = 53 | issue = 2 | pages = 356-8 | month = Feb | year = 1999 | doi = | PMID = 9933054 }}</ref>
***One study suggests hypoechoic lesions tend to have a worse outcome;<ref name=pmid22920545>{{Cite journal | last1 = Nakano Junqueira | first1 = VC. | last2 = Zogbi | first2 = O. | last3 = Cologna | first3 = A. | last4 = Dos Reis | first4 = RB. | last5 = Tucci | first5 = S. | last6 = Reis | first6 = LO. | last7 = Westphalen | first7 = AC. | last8 = Muglia | first8 = VF. | title = Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? | journal = Ultrasound Med Biol | volume = 38 | issue = 10 | pages = 1689-94 | month = Oct | year = 2012 | doi = 10.1016/j.ultrasmedbio.2012.06.006 | PMID = 22920545 }}</ref> however, this is not supported by an older study.<ref name=pmid1688955>{{Cite journal | last1 = Devonec | first1 = M. | last2 = Fendler | first2 = JP. | last3 = Monsallier | first3 = M. | last4 = Mouriquand | first4 = P. | last5 = Maquet | first5 = JH. | last6 = Mestas | first6 = JL. | last7 = Dutrieux-Berger | first7 = N. | last8 = Perrin | first8 = P. | title = The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. | journal = J Urol | volume = 143 | issue = 2 | pages = 316-9 | month = Feb | year = 1990 | doi = | PMID = 1688955 }}</ref>

===Prostatectomy grossing===
{{Main|Radical prostatectomy}}

===Cytoprostatectomy grossing===
{{Main|Cystoprostatectomy grossing}}
*Limited sampling of the prostate may lead to undersampling error.<ref name=pmid11182038>{{Cite journal | last1 = Cindolo | first1 = L. | last2 = Benincasa | first2 = G. | last3 = Autorino | first3 = R. | last4 = Domizio | first4 = S. | last5 = De Rosa | first5 = G. | last6 = Testa | first6 = G. | last7 = D'Armiento | first7 = M. | last8 = Altieri | first8 = V. | title = Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study. | journal = Oncol Rep | volume = 8 | issue = 2 | pages = 269-71 | month = | year = | doi = | PMID = 11182038 }}</ref>

==Microscopic==
===Criteria as a list===
Major criteria (the ABCs of prostate pathology):<ref name=pmid17213347>{{cite journal |author=Humphrey PA |title=Diagnosis of adenocarcinoma in prostate needle biopsy tissue |journal=J. Clin. Pathol. |volume=60 |issue=1 |pages=35–42 |year=2007 |month=January |pmid=17213347 |pmc=1860598 |doi=10.1136/jcp.2005.036442 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed}}</ref>
#Architecture.
#*Increased gland density.
#*Small circular glands.
#**In rare subtypes - large branching glands.
#*"Infiltrative growth" pattern - malignant glands between benign ones.
#**Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f1.html#figure-title Infiltrative growth pattern (nature.com)].
#Basal cells lacking.
#Cytological abnormalities:
#*Nuclear enlargement (subtle).
#*[[Nucleoli]] (prominent).

Minor criteria:<ref name=pmid17213347/>
#Nuclear hyperchromasia.
#Wispy blue mucin.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f3.html#figure-title Wispy blue mucin (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Pink amorphous secretions.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html Pink amorphous secretions (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Intraluminal crystalloid.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f4.html#figure-title Intraluminal crystalloid (nature.com)] - from Epstein.<ref name=pmid14739905/>
#Amphophilic cytoplasm.
#*Amphopilic is said to be ''bluish-red''<ref>URL: [http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref> -- though might also be described as ''blue-grey''.
#**Image: [http://www.webpathology.com/image.asp?n=4&Case=20 Amphophilic cytoplasm is prostate carcinoma].
#Adjacent [[HGPIN]].
#Mitoses - quite rare.

Extent/quantity criteria:
*There is no agreed upon minimum number of glands; however, one paper suggests that agreement among experts is low with 5 or less glands.<ref name=pmid20061936>{{Cite journal | last1 = Van der Kwast | first1 = TH. | last2 = Evans | first2 = A. | last3 = Lockwood | first3 = G. | last4 = Tkachuk | first4 = D. | last5 = Bostwick | first5 = DG. | last6 = Epstein | first6 = JI. | last7 = Humphrey | first7 = PA. | last8 = Montironi | first8 = R. | last9 = Van Leenders | first9 = GJ. | title = Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 169-77 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c7997b | PMID = 20061936 }}</ref>
**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>

Features considered pathognomonic for prostate carcinoma by some authorities:<ref name=pmid16613324>{{Cite journal | last1 = Egevad | first1 = L. | last2 = Allsbrook | first2 = WC. | last3 = Epstein | first3 = JI. | title = Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists. | journal = Hum Pathol | volume = 37 | issue = 3 | pages = 292-7 | month = Mar | year = 2006 | doi = | PMID = 16613324 }}</ref><ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref>
#Perineural invasion.
#*Must be circumferential (>95% of circumference{{fact}}).
#Glomeruloid bodies.
#[[Collagenous micronodules]] also known as ''mucinous fibroplasia''.

<gallery>
Image: Intraluminal eosinophilic crystalloid of prostate gland - high mag.jpg| Intraluminal eosinophilic crystalloid - high mag. (WC)
Image: Prostate carcinoma with blue mucin -- very high mag.jpg | Whispy blue mucin - very high mag. (WC)
Image: Prostate carcinoma with blue mucin - a1 -- intermed mag.jpg | Whispy blue mucin - intermed. mag. (WC)
</gallery>

===Divided into high and low power===
====Low power features====
*Architecture is the '''key''' to diagnosing low grade cancer.
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Sharp transition between gland border and lumen.
***Loss of epithelial folding at the epithelium-gland lumen interface - "punched-out" appearance.
**Eosinophilic debris within the gland lumen (pink amorphous secretions, intraluminal crystalloid).
**Blue-tinged acellular material within the gland lumen (mucin) -- uncommon.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.

====High power features====
*Nuclear changes.
**Hyperchromatic nuclei (like in HGPIN).
**Nuclear enlargement, mild (10%?).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult/impossible to see at low power.
*"Large" nucleoli.
**Visible on intermediate and high power (100x / 200x magnification).
***May be difficult to see - especially if light intensity is low or the staining is of poor quality.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk over-calling something benign).
**"Large" is rarely precisely quantified; 3 micrometres has been suggested as "large" based on one study.<ref name=pmid1688728>{{Cite journal | last1 = Kelemen | first1 = PR. | last2 = Buschmann | first2 = RJ. | last3 = Weisz-Carrington | first3 = P. | title = Nucleolar prominence as a diagnostic variable in prostatic carcinoma. | journal = Cancer | volume = 65 | issue = 4 | pages = 1017-20 | month = Feb | year = 1990 | doi = | PMID = 1688728 }}</ref>
***Three micrometres is a little more than 1/3 of [[RBC]] diameter.
*Loss of basal cells - diagnostic feature.
**Like in [[breast pathology]] (where one looks for loss of myoepithelial cells) - this may be difficult to see.

Notes:
*Mitoses are not a common feature.
**If you find them the lesion is probably high-grade.
**Generally, it isn't worth looking for them.

===Mimics===
Mimics of prostate adenocarcinoma:<ref>{{Ref TPoSP|100-3}}</ref>
{| class="wikitable sortable"
! Entity
! Key feature
! Detailed microscopic
! Other
! Image
|-
| Adenosis ([[AKA]] ''atypical adenomatous hyperplasia'')
| gradual transition between normal & small gland (NOT two populations)
| many small glands, lack nuclear size variation, basal layer present
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| [[Image:Adenosis of prostate_--_intermed_mag.jpg|thumb|150px|center| Adenosis of prostate. (WC)]]
|-
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| analogous to [[sclerosing adenosis of the breast]]{{fact}}
| [http://webpathology.com/image.asp?case=21&n=40 Sclerosing adenosis (webpathology.com)]
|-
| [[atrophy of the prostate|Atrophy]]
| sharp angulation of gland
| nuclear hyperchromasia, scant cytoplasm
| may appear right beside non-atrophic tissue
| [[Image:Atrophic_prostatic_glands_--_high_mag.jpg|thumb|150px|center| Prostatic atrophy. (WC)]]
|-
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
| two distinct cell populations (in epithelial component)
| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| [[Image:Basal_cell_hyperplasia_of_prostate_-_high_mag.jpg|thumb|150px|center| Prostatic BCH. (WC)]]
|-
| [[Bulbourethral gland]]
| no nuclear atypia
| clear cytoplasm
| apex of prostate
| [[Image:Bulbourethral gland -- very high mag.jpg |thumb|150px|center| Bulbourethral gland. (WC)]]
|-
| [[Seminal vesicles]] / ejaculatory ducts
| lipofuscin (yellow granular material in cytoplasm), smudge cells (smeared appearance + hyperchromatic)
| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| [[Image:Seminal_vesicle_high_mag.jpg |thumb|150px|center|Seminal vesicles. (WC)]]
|-
| [[Radiation effect]]
| marked nuclear size variation
| increased stroma (fibrosis), lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of [[postradiation prostatic carcinoma|postradiation cancer]]
| [[Image:Prostate_with_radiation_changes_--_high_mag.jpg|thumb|150px|center|Radiation change. (WC)]]
|-
| Prostatitis
| inflammatory cells (lymphocytes, plasma cells, PMNs)
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| [[Image:Inflammation_of_prostate.jpg|thumb|150px|center| Prostatic inflammation. (WC)]]
|-
| [[Vasitis nodosa]]
| sperm within ducts, clinical history (usu. post-[[vasectomy]])
| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| [[Image:Vasitis nodosa -11- intermed mag.jpg|thumb|150px|center| VN. (WC)]]
|}
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.

===Situations where prostate adenocarcinoma may be missed===
Key reasons for false negative prostate samples<ref>{{cite journal |vauthors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}}</ref>:
*Tissue artefacts (try levels and/or IHC):
**Crush artefact
**Thick sections
**Aberrant H&E staining
**Freezing artefact
**Cautery
*Minimal adenocarcinoma (less than 1mm long or involving less than 5% of a core biopsy):
*Prostatic adenocarcinoma variants that mimic benign:
**[[Atrophic prostate carcinoma]]
**[[Pseudohyperplastic adenocarcinoma]]
**[[Foamy gland adenocarcinoma]]
**[[PIN-like adenocarcinoma]]
**Microcystic adenocarcinoma
*Single cells of Gleason 5 adenocarcinoma (missed or mistaken for lymphocytes; try IHC)
*Treatment effect (check clinical information and look for treatment effect in benign glands)

===Prostate cancer grading===
{{Main|Prostate cancer grading}}
It covers the ''Gleason grading system'' and the (new) ''prognostic grade groupings''.

===Staging parameters, margins and more===
====Surgical margins====
{{Main|Surgical margins}}
*Positive is ''tumour touching [[ink]]''.† <ref name=pmid22578729>{{Cite journal | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
**"Close" margins (<0.1 mm) have an increased recurrence risk.<ref name=pmid22578729/>

Notes:
*Surgical margin - where the surgeon cut.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
* † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.<ref>URL: [http://urology.jhu.edu/newsletter/prostate_cancer410.php http://urology.jhu.edu/newsletter/prostate_cancer410.php]. Accessed on: 26 March 2013.</ref>

=====Rates and implication=====
Positivity rate varies substantially (13-44%):
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*France: 13-17% -- PSA and prostate size predictors of positivity.<ref name=pmid22860572>{{Cite journal | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>

Note:
*Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.<ref name=pmid22860630/>

The impact of positive margins:
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Bladder neck margin positivity may change the T-stage - see below.

=====Bladder neck margin=====
{{Main|Bladder neck invasion}}
:[[AKA]] ''invasion of the bladder neck''.<ref name=pmid19914651/>
*Bladder neck margin positivity typically is '''pT3a'''.<ref name=pmid23225909>{{Cite journal | last1 = Chung | first1 = MS. | last2 = Lee | first2 = SH. | last3 = Lee | first3 = DH. | last4 = Chung | first4 = BH. | title = Evaluation of the 7th American Joint Committee on cancer TNM staging system for prostate cancer in point of classification of bladder neck invasion. | journal = Jpn J Clin Oncol | volume = 43 | issue = 2 | pages = 184-8 | month = Feb | year = 2013 | doi = 10.1093/jjco/hys196 | PMID = 23225909 }}</ref>
*Seen in approximately 1% of prostatectomies.<ref name=pmid19914651>{{Cite journal | last1 = Pierorazio | first1 = PM. | last2 = Epstein | first2 = JI. | last3 = Humphreys | first3 = E. | last4 = Han | first4 = M. | last5 = Walsh | first5 = PC. | last6 = Partin | first6 = AW. | title = The significance of a positive bladder neck margin after radical prostatectomy: the American Joint Committee on Cancer Pathological Stage T4 designation is not warranted. | journal = J Urol | volume = 183 | issue = 1 | pages = 151-7 | month = Jan | year = 2010 | doi = 10.1016/j.juro.2009.08.138 | PMID = 19914651 }}</ref>

====Extraprostatic extension====
:Abbreviated ''EPE''.
{{Main|Prostate cancer staging#Extraprostatic extension}}

====Seminal vesicle invasion====
:Abbreviated ''SVI''.
{{Main|Prostate cancer staging#Seminal vesicle invasion}}

====Perineural invasion====
{{Main|Perineural invasion}}
*''Not'' a staging parameter.
*Seen in approximately 20% of core biopsies.<ref name=pmid16096404>{{Cite journal | last1 = Ali | first1 = TZ. | last2 = Epstein | first2 = JI. | title = Perineural involvement by benign prostatic glands on needle biopsy. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1159-63 | month = Sep | year = 2005 | doi = | PMID = 16096404 }}</ref>
*Complete wrapping of a nerve by epithelium is considered pathognomonic for cancer.<ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref><ref name=pmid16096404/>

Note:
*Occasionally, benign glands are found perineural.<ref name=pmid16096404/>
**These should ''not'' completely wrap around the nerve and should be cytologically benign.

==IHC==
===General recommendations===
ISUP consensus statement:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*Should ''not'' be used if cancer is obvious.
*Should ''not'' be used if it isn't going change the clinical management.

===Prostate markers===
*[[PSA]] (prostate specific antigen) +ve.
*[[PSAP]] (prostatic specific acid phosphatase) +ve. †
*P501S +ve. ‡
*[[NKX3.1]] +ve. ‡

Notes:
*† PSAP may be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref>
*‡ P501S and NKX3.1 are considered second line markers.<ref name=pmid25025364/>
*Prostate carcinoma is typically CK7 -ve and CK20 -ve; however, in high [[Gleason score]] cancers focal positivity of these markers can be seen.<ref name=pmid11888088>{{Cite journal | last1 = Goldstein | first1 = NS. | title = Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. | journal = Am J Clin Pathol | volume = 117 | issue = 3 | pages = 471-7 | month = Mar | year = 2002 | doi = 10.1309/G6PR-Y774-X738-FG2K | PMID = 11888088 }}</ref>
**CK7: >25-50% staining seen in ~5% of cases.
***>50% staining with CK7 is not report.
**CK20: >25-50% staining seen in ~10% of cases.
***>50% staining with CK20 is not reported.

===Benign prostate versus neoplastic prostate===
*AMACR +ve.
*p63 -ve.
*HMWCK (34betaE12) -ve.

Combination immunostains:
*''PIN-4'' -- consists of: CK5 + CK14 + p63 + P504S (AMACR).<ref>URL: [http://biocare.net/wp-content/uploads/225DS.pdf http://biocare.net/wp-content/uploads/225DS.pdf]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/ http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.webpathology.com/image.asp?case=96&n=5 http://www.webpathology.com/image.asp?case=96&n=5]. Accessed on: 18 October 2011.</ref>
**[[AKA]] ''PIN''.
**[[AKA]] ''CAP''.
***Why '''CAP'''?
****A. '''CA'''ncer of the '''P'''rostate.

Other IHC stains:
*AR +ve -- in prostate confined cancer.
**Usually -ve in lymph node +ve disease.<ref name=pmid20878946>{{Cite journal | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>

Note:
*Bcl-2 marks basal cells in prostate cancer.<ref name=pmid20189848>{{Cite journal | last1 = Boran | first1 = C. | last2 = Kandirali | first2 = E. | last3 = Yilmaz | first3 = F. | last4 = Serin | first4 = E. | last5 = Akyol | first5 = M. | title = Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma. | journal = Urol Oncol | volume = 29 | issue = 6 | pages = 614-23 | month = | year = | doi = 10.1016/j.urolonc.2009.11.013 | PMID = 20189848 }}</ref>

====Prostate carcinoma versus urothelial carcinoma====
The ISUP panel recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*PSA +ve (-ve in UCC).
*GATA3 -ve (+ve in UCC).

Another panel - if GATA3 isn't available:
*Prostate: PSA +ve, p63 -ve, HWMCK -ve.
*Urothelial: p63 +ve, HWMCK +ve, PSA -ve.

Notes:
*AMACR not useful; it is positive in ~50% of [[UCC]].<ref name=pmid16315020>{{Cite journal | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*CK7 and CK20 are typically negative in prostate carcinoma, and classically positive in urothelial carcinoma.
*CK34betaE12 may be positive in prostate cancer; 43% of cases in one small series of cases with lymph node metastases.<ref name=pmid9024071>{{Cite journal | last1 = Googe | first1 = PB. | last2 = McGinley | first2 = KM. | last3 = Fitzgibbon | first3 = JF. | title = Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma. | journal = Am J Clin Pathol | volume = 107 | issue = 2 | pages = 219-23 | month = Feb | year = 1997 | doi = | PMID = 9024071 }}</ref>

===Rate of utilization===
*Dependent on practise setting.
**One tertiary academic institution uses it on ~ 40% of cases.<ref>{{Cite journal | last1 = Watson | first1 = K. | last2 = Wang | first2 = C. | last3 = Yilmaz | first3 = A. | last4 = Bismar | first4 = TA. | last5 = Trpkov | first5 = K. | title = Use of immunohistochemistry in routine workup of prostate needle biopsies: a tertiary academic institution experience. | journal = Arch Pathol Lab Med | volume = 137 | issue = 4 | pages = 541-5 | month = Apr | year = 2013 | doi = 10.5858/arpa.2012-0145-OA | PMID = 23273390 }}</ref>

==Molecular changes in prostate cancer==
A fusion gene between ''TMPRSS2'' and ''ERG'' is described.<ref name=pmid20478527>{{cite journal | author = Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM | title = An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression | journal = Cancer Cell | volume = 17 | issue = 5 | pages = 443–54 | year = 2010 | month = May | pmid = 20478527 | pmc = 2874722 | doi = 10.1016/j.ccr.2010.03.018 | url = }}</ref><ref name=omim602060>{{OMIM|602060}}</ref>
*Both genes are on chromosome 21.
*Currently ''not'' used diagnostically.
*Fusion gene seen in approximately 50% of prostate cancer.<ref name=omim602060>{{OMIM|602060}}</ref>
*A subset of ''TMPRSS2-ERG'' known as ''2+Edel'' (seen in ~7% of all prostate cancer cases) predicts poor survival.<ref name=pmid17637754>{{Cite journal | last1 = Attard | first1 = G. | last2 = Clark | first2 = J. | last3 = Ambroisine | first3 = L. | last4 = Fisher | first4 = G. | last5 = Kovacs | first5 = G. | last6 = Flohr | first6 = P. | last7 = Berney | first7 = D. | last8 = Foster | first8 = CS. | last9 = Fletcher | first9 = A. | title = Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. | journal = Oncogene | volume = 27 | issue = 3 | pages = 253-63 | month = Jan | year = 2008 | doi = 10.1038/sj.onc.1210640 | PMID = 17637754 }}</ref>

==Sign out==
===Prostatectomy specimens===
*A prostatectomy that appears to be negative should be worked-up. This is discuss in the ''[[negative prostatectomy]]'' article.
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP checklist].

<pre>
A. LYMPH NODES, RIGHT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

B. LYMPH NODES, LEFT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

C. PROSTATE GLAND AND SEMINAL VESICLES, RADICAL PROSTATECTOMY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4), pT2c pN0.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>

===Transurethral resection of prostate===
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 6/10 (3+3);
-- Approximately 2% of tissue involved;
-- Please see tumour summary.

Comment:
The World Health Organization (WHO) grade is: 1 out of 5.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 7/10 (3+4);
-- Approximately 4% of tissue involved;
-- Please see tumour summary.
- Benign inflamed urothelium.

Comment:
The World Health Organization (WHO) grade is: 2 out of 5. Gleason pattern 3 represents 90% of the tumour, and Gleason pattern 4 represents 10% of the tumour.
</pre>

====Block letters====
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.

TUMOUR SUMMARY - TRANSURETHRAL RESECTION OF PROSTATE (TURP).

PROCEDURE: TRANSURETHRAL PROSTATIC RESECTION.
SPECIMEN SIZE: WEIGHT: 10 GRAMS.
HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).

HISTOLOGIC GRADING:
PRIMARY PATTERN: 3.
SECONDARY PATTERN: 4 (40% OF TUMOUR).
TOTAL GLEASON SCORE: 7 (3+4).

TUMOUR QUANTITATION - PERCENTAGE OF PROSTATIC TISSUE INVOLVED BY TUMOUR: 80 %.

PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
SEMINAL VESICLE INVASION: NOT IDENTIFIED.
LYMPH-VASCULAR INVASION: NOT IDENTIFIED.
PERINEURAL INVASION: NOT IDENTIFIED.

ADDITIONAL PATHOLOGIC FINDINGS:
HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).
NODULAR PROSTATIC HYPERPLASIA.
CHRONIC INFLAMMATION.
</pre>

<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- Adenocarcinoma, Gleason score 7 (3+4)
- Approximately 3% of sampled tissue involved
- Please see tumour summary

Tumour summary:
Procedure: Transurethral resection of prostate
Specimen weight: 11.7 g
Histologic type: Adenocarcinoma, acinar type

Histologic grade:
Primary pattern: 3
Secondary pattern: 4 (<15% of tumor)
Total Gleason score: 7/10 (3+4)

Tumor volume: 3% of tissue

Periprostate fat invasion: Periprostatic fat not identified
Seminal vesicle invasion: Seminal vesicle not identified
Lymphovascular inasion: Not identified
Perineural invasion: Not identified

Additional findings:
Glandular and stromal hyperplasia
Mild chronic inflammation
</pre>

===Biopsy specimens===
Important elements - a list:<ref name=pmid17213347/>
#Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
#Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
#Number of cores and number involved, e.g. "2/3 cores involved by cancer".
#Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour". ‡
#Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
#Presence of [[perineural invasion]].
#Presence of extension into fat (extraprostatic extension).

Notes:
*‡ "Percent area involved" may seem like an odd thing to request 'cause it is sampling dependent, i.e. if the radiologist sticks the biopsy needle deeper into the lesion more of the core is positive, but urologists think it is important -- more important than perineural invasion.<ref name=pmid15223967>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.<ref name=pmid22688447>{{Cite journal | last1 = Fu | first1 = Q. | last2 = Moul | first2 = JW. | last3 = Bañez | first3 = LL. | last4 = Sun | first4 = L. | last5 = Mouraviev | first5 = V. | last6 = Xie | first6 = D. | last7 = Polascik | first7 = TJ. | title = Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer. | journal = Med Oncol | volume = 29 | issue = 5 | pages = 3339-44 | month = Dec | year = 2012 | doi = 10.1007/s12032-012-0270-4 | PMID = 22688447 }}</ref>

====Completely negative====
<pre>
A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

C. PROSTATE, RIGHT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

D. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

E. PROSTATE, RIGHT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

I. PROSTATE, LEFT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

J. PROSTATE, LEFT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

K. PROSTATE, LEFT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
</pre>

====Negative biopsy in surveillance====
<pre>
COMMENT:
The previous results are noted. The absence of cancer in this biopsy may
be due to sampling.
</pre>

====No glands====
<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN FIBROMUSCULAR TISSUE;
- NO PROSTATIC GLANDULAR TISSUE PRESENT.
</pre>

====Inflammation====
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- ACUTE AND CHRONIC INFLAMMATION.
</pre>

====Positive====
<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 25% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

=====Tumour summaries=====
*These are not completely without controversy.
*It should be noted that treatment is driven by the highest Gleason score.{{fact}}

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- TOTAL GLEASON SCORE: 7.
- PRIMARY PATTERN: 4.
- SECONDARY PATTERN: 3.
- PERCENT OF TUMOUR WITH PATTERN HIGHER THAN GRADE 3: 75%.

- NUMBER OF CORES POSITIVE: 10.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 152 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 44%.

- PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: SEMINAL VESICLE NOT IDENTIFIED.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- PERINEURAL INVASION: PRESENT.

- ADDITIONAL FINDINGS: HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA, CHRONIC INFLAMMATION (FOCAL).
</pre>

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- HIGHEST GLEASON SCORE: 8 (4+4).
- SUMMARY GLEASON SCORE: 7 (4+3).
- PERCENT OF TUMOUR WITH PATTERN 4: 55%.
- PERCENT OF TUMOUR WITH PATTERN 5: 0%.

- NUMBER OF CORES POSITIVE: 12.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 178 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 80%.

- PERINEURAL INVASION: PRESENT.
- PERIPROSTATIC FAT INVASION: PRESENT.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: NOT IDENTIFIED.
</pre>

===Seminal vesicle/ejaculatory duct invasion on biopsy===
<pre>
COMMENT:
The seminal vesicles and ejaculatory ducts have the same histology; thus, it is not
usually possible to confidently differentiate them in a needle biopsy.

SV/ED invasion was demonstrated with CK7, CK34betaE12/AMACR, PSA and p63 immunostaining.
The tumour is PSA and AMACR positive.
</pre>

=Intraductal spread of prostate cancer=
==Intraductal carcinoma of the prostate==
*[[AKA]] ''[[intraductal carcinoma]]''.
*[[AKA]] ''intraductal prostate carcinoma''.
{{Main|Intraductal carcinoma of the prostate}}

=Unusual forms of prostate cancer=
==Prostatic ductal adenocarcinoma==
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
{{Main|Ductal adenocarcinoma of the prostate gland}}

==PIN-like prostatic ductal adenocarcinoma==
{{Main|High-grade prostatic intraepithelial neoplasia-like ductal adenocarcinoma of the prostate}}

==Foamy gland carcinoma==
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862>{{Cite journal | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
{{Main|Foamy gland carcinoma}}

==Atrophic prostate carcinoma==
*[[AKA]] ''atrophic carcinoma''.
{{Main|Atrophic prostate carcinoma}}

==Mucinous prostate carcinoma==
{{Main|Mucinous adenocarcinoma of the prostate}}

==Pseudohyperplastic prostatic adenocarcinoma==
*[[AKA]] ''pseudohyperplastic adenocarcinoma''.
{{Main|Pseudohyperplastic prostatic adenocarcinoma}}

==Prostatic signet ring cell carcinoma==
{{Main|Signet ring cell carcinoma}}
===General===
*Very rare - 9 cases in a series of 29,783 prostate cancer cases.<ref name=pmid21123640>{{Cite journal | last1 = Warner | first1 = JN. | last2 = Nakamura | first2 = LY. | last3 = Pacelli | first3 = A. | last4 = Humphreys | first4 = MR. | last5 = Castle | first5 = EP. | title = Primary signet ring cell carcinoma of the prostate. | journal = Mayo Clin Proc | volume = 85 | issue = 12 | pages = 1130-6 | month = Dec | year = 2010 | doi = 10.4065/mcp.2010.0463 | PMID = 21123640 }}</ref>
*Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.<ref name=pmid21123640/>

===Microscopic===
Features:
*Signet ring cells - see ''[[basics]]'' article.

DDx:
*Acinar adenocarcinoma - Gleason pattern 4 with very small glands.

====Images====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRCC (nih.gov)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f7.html#figure-title Prostatic SRCC (nature.com)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f8.html Prostatic SRCC (nature.com)].
*[http://www.webpathology.com/image.asp?case=23&n=34 Prostatic SRCC (webpathology.com)] - looks like ''acinar adenocarcinoma''.

===Stains===
*Alcian blue-PAS stain +ve.
*[[PAS stain|PAS]] -- 50% of cases +ve.<ref name=pmid21123640/>
*[[Alcian blue stain|Alcian blue]] -- 44% of cases +ve.<ref name=pmid21123640/>

==Sarcomatoid carcinoma of the prostate==
{{Main|Sarcomatoid carcinoma of the prostate}}

==Small cell carcinoma of the prostate gland==
{{Main|Small cell carcinoma of the prostate gland}}

==Adenoid cystic/basal cell carcinoma of the prostate==
*Abbreviated ''ACBCC''.
{{Main|Adenoid cystic/basal cell carcinoma of the prostate}}

==Postradiation prostate cancer==
{{Main|Postradiation prostate cancer}}

=Metastatic disease and other cancers of the prostate=
==Urothelial carcinoma==
{{Main|Urothelial carcinoma of the urethra}}

=See also=
*[[Prostate gland]].
*[[Genitourinary pathology]]

=References=
{{Reflist|2}}

[[Category:Genitourinary pathology]]
[[Category:Prostate carcinoma]]

User:Sarah A

2020-03-05T15:57:08Z

Sarah A: /* Edits to work on: */

Prostate cancer

2020-03-05T15:46:43Z

{{ Infobox diagnosis
| Name = Prostate carcinoma
| Image = Prostate cancer with Gleason pattern 4 low mag.jpg
| Width =
| Caption = Prostate carcinoma. [[H&E stain]].
| Micro = major criteria: abnormal architecture (increased gland density, usu. small circular glands, "infiltrative growth" pattern), basal cells lost, cytological abnormalities (nuclear enlargement, nucleoli); minor criteria: nuclear hyperchromasia, wispy blue mucin, pink amorphous secretions, intraluminal crystalloid, amphophilic cytoplasm, adjacent [[HGPIN]], mitoses
| Subtypes =
| LMDDx = [[high-grade prostatic intraepithelial neoplasia]], [[atypical small acinar proliferation]] (biopsy only), [[prostatic atrophy]], [[seminal vesicle]], [[basal cell hyperplasia of the prostate|basal cell hyperplasia]], others
| Stains =
| IHC = PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
| EM =
| Molecular = +/-[[BRCA1]] mutation (genetic predisposition), +/-[[BRCA2]] mutation (genetic predisposition)
| IF =
| Gross = usu. posterior aspect of the prostate - often not apparent at gross
| Grossing = [[prostate biopsy]], [[prostate chips]], [[radical prostatectomy]]
| Staging = [[prostate cancer staging]]
| Site = [[prostate gland]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs = firm, nodular prostate on digital rectal exam
| Symptoms = often asymptomatic
| Prevalence = very common
| Bloodwork = PSA elevated (common)
| Rads = hypoechoic areas, no apparent abnormality
| Endoscopy =
| Prognosis = good-to-poor (depends on [[prostate cancer grading|grade (Gleason score)]] and [[stage]])
| Other =
| ClinDDx = [[prostatitis]], [[nodular hyperplasia of the prostate]]
| Tx = observation (common for low-grade, low tumour burden), radiation or radical prostatectomy
}}
This article deals with '''prostate [[cancer]]'''.

The vast majority of prostate cancers are carcinomas and could be labelled '''prostatic carcinoma'''. Most prostatic carcinomas are gland forming; thus, they can be labelled '''prostatic [[adenocarcinoma]]''' or '''adenocarcinoma of the prostate'''.

Benign pathology of the prostate gland, and prostate histology and anatomy are dealt with in the ''[[prostate gland]]'' article.

=Conventional prostate cancer=
==General==
*Very common.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.<ref>{{cite journal |author=Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD |title=The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients |journal=J. Urol. |volume=150 |issue=2 Pt 1 |pages=379–85 |year=1993 |month=August |pmid=8326560 |doi= |url=}}</ref>{{fact}}
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.

*Risk increased with a [[BRCA1]] or [[BRCA2]] mutation<ref name=pmid23747895>{{Cite journal | last1 = Li | first1 = D. | last2 = Kumaraswamy | first2 = E. | last3 = Harlan-Williams | first3 = LM. | last4 = Jensen | first4 = RA. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Front Biosci (Landmark Ed) | volume = 18 | issue = | pages = 1445-59 | month = | year = 2013 | doi = | PMID = 23747895 }}</ref> - families have a mix of [[breast cancer]] and prostate cancer.
**BRCA2 mutation risk >8x for men over 65 years old.<ref name=pmid22522501>{{Cite journal | last1 = Castro | first1 = E. | last2 = Eeles | first2 = R. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Asian J Androl | volume = 14 | issue = 3 | pages = 409-14 | month = May | year = 2012 | doi = 10.1038/aja.2011.150 | PMID = 22522501 }}</ref>
**A BRCA2 founder mutation is described in French Canadians.<Ref name=pmid23318356>{{Cite journal | last1 = Taherian | first1 = N. | last2 = Hamel | first2 = N. | last3 = Bégin | first3 = LR. | last4 = Bismar | first4 = TA. | last5 = Goldgar | first5 = DE. | last6 = Feng | first6 = BJ. | last7 = Foulkes | first7 = WD. | title = Familial prostate cancer: the damage done and lessons learnt. | journal = Nat Rev Urol | volume = 10 | issue = 2 | pages = 116-22 | month = Feb | year = 2013 | doi = 10.1038/nrurol.2012.257 | PMID = 23318356 }}</ref>

===Management===
====Dirty first approximation====
*The management changes between [[Gleason score]] 6, 7 (3+4), 7 (4+3) and 8.

Typically, the implications are:
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 7 with a bit of Gleason pattern 4 and a low tumour volume: it is reasonable to watch ''or'' do something. ‡
* Gleason 7 with a lot of Gleason pattern 4 ''or'' a high tumour volume: do something -- surgery ''or'' radiation therapy.
* Gleason 8+: bad cancer -- do something quickly!

Note:
* ‡ It has been said that ''Gleason score 7 with a bit of Gleason pattern 4 is the new Gleason score 6''.

Bottom line:
*You want to be sure when you call something Gleason pattern 4.

====Observational strategies====
*Delay of definitive treatment (surgery ''or'' radiation).
*Common in the management of prostate cancer.

Classification:<ref name=pmid23126653>{{Cite journal | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume = | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi = | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
*Active surveillance (AS).
**Low risk of progression.
**May get definitive treatment later.
*Watchful waiting (WW).
**Higher risk of progression.

Note:
*There is no agreed upon set of criteria for active surveillance, and the large number of criteria out there vary significantly.<ref name=pmid22314081>{{Cite journal | last1 = Palisaar | first1 = JR. | last2 = Noldus | first2 = J. | last3 = Löppenberg | first3 = B. | last4 = von Bodman | first4 = C. | last5 = Sommerer | first5 = F. | last6 = Eggert | first6 = T. | title = Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. | journal = BJU Int | volume = 110 | issue = 6 Pt B | pages = E172-81 | month = Sep | year = 2012 | doi = 10.1111/j.1464-410X.2012.10935.x | PMID = 22314081 }}</ref>

=====Active surveillance=====
The ''Klotz'' criteria for active surveillance - pathologic factors only:<ref name=pmid22314081/><ref>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for prostate cancer: for whom? | journal = J Clin Oncol | volume = 23 | issue = 32 | pages = 8165-9 | month = Nov | year = 2005 | doi = 10.1200/JCO.2005.03.3134 | PMID = 16278468 }}</ref>
*Gleason score 6 or less.
*All biopsies cores < 50% involvement.
*One or two cores involved.<ref>URL: [http://www.active-surveillance.com/laurence-klotz-md/ http://www.active-surveillance.com/laurence-klotz-md/]. Accessed on: 12 July 2013.</ref><ref name=pmid23548978>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance: patient selection. | journal = Curr Opin Urol | volume = 23 | issue = 3 | pages = 239-44 | month = May | year = 2013 | doi = 10.1097/MOU.0b013e32835f8f6b | PMID = 23548978 }}</ref><ref name=pmid22891078>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for low-risk prostate cancer. | journal = F1000 Med Rep | volume = 4 | issue = | pages = 16 | month = | year = 2012 | doi = 10.3410/M4-16 | PMID = 22891078 | PMC = 3412317 }}</ref>
Clinical criteria:
*PSA <= 10 ng/mL.<ref name=pmid22314081/>
*Negative DRE.

==Gross==
*Prostate cancer is uncommonly apparent on gross.
*Classic location: posterior aspect of the prostate.

===Radiology===
*Hypoechoic areas = suspicious for cancer.
**It seems that size of the area matters.
***Small hypoechoic areas (<0.2 cm3) have cancer less than 4% of the time.<ref name=pmid9933054>{{Cite journal | last1 = Fleshner | first1 = NE. | last2 = O'Sullivan | first2 = M. | last3 = Premdass | first3 = C. | last4 = Fair | first4 = WR. | title = Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL. | journal = Urology | volume = 53 | issue = 2 | pages = 356-8 | month = Feb | year = 1999 | doi = | PMID = 9933054 }}</ref>
***One study suggests hypoechoic lesions tend to have a worse outcome;<ref name=pmid22920545>{{Cite journal | last1 = Nakano Junqueira | first1 = VC. | last2 = Zogbi | first2 = O. | last3 = Cologna | first3 = A. | last4 = Dos Reis | first4 = RB. | last5 = Tucci | first5 = S. | last6 = Reis | first6 = LO. | last7 = Westphalen | first7 = AC. | last8 = Muglia | first8 = VF. | title = Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? | journal = Ultrasound Med Biol | volume = 38 | issue = 10 | pages = 1689-94 | month = Oct | year = 2012 | doi = 10.1016/j.ultrasmedbio.2012.06.006 | PMID = 22920545 }}</ref> however, this is not supported by an older study.<ref name=pmid1688955>{{Cite journal | last1 = Devonec | first1 = M. | last2 = Fendler | first2 = JP. | last3 = Monsallier | first3 = M. | last4 = Mouriquand | first4 = P. | last5 = Maquet | first5 = JH. | last6 = Mestas | first6 = JL. | last7 = Dutrieux-Berger | first7 = N. | last8 = Perrin | first8 = P. | title = The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. | journal = J Urol | volume = 143 | issue = 2 | pages = 316-9 | month = Feb | year = 1990 | doi = | PMID = 1688955 }}</ref>

===Prostatectomy grossing===
{{Main|Radical prostatectomy}}

===Cytoprostatectomy grossing===
{{Main|Cystoprostatectomy grossing}}
*Limited sampling of the prostate may lead to undersampling error.<ref name=pmid11182038>{{Cite journal | last1 = Cindolo | first1 = L. | last2 = Benincasa | first2 = G. | last3 = Autorino | first3 = R. | last4 = Domizio | first4 = S. | last5 = De Rosa | first5 = G. | last6 = Testa | first6 = G. | last7 = D'Armiento | first7 = M. | last8 = Altieri | first8 = V. | title = Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study. | journal = Oncol Rep | volume = 8 | issue = 2 | pages = 269-71 | month = | year = | doi = | PMID = 11182038 }}</ref>

==Microscopic==
===Criteria as a list===
Major criteria (the ABCs of prostate pathology):<ref name=pmid17213347>{{cite journal |author=Humphrey PA |title=Diagnosis of adenocarcinoma in prostate needle biopsy tissue |journal=J. Clin. Pathol. |volume=60 |issue=1 |pages=35–42 |year=2007 |month=January |pmid=17213347 |pmc=1860598 |doi=10.1136/jcp.2005.036442 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed}}</ref>
#Architecture.
#*Increased gland density.
#*Small circular glands.
#**In rare subtypes - large branching glands.
#*"Infiltrative growth" pattern - malignant glands between benign ones.
#**Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f1.html#figure-title Infiltrative growth pattern (nature.com)].
#Basal cells lacking.
#Cytological abnormalities:
#*Nuclear enlargement (subtle).
#*[[Nucleoli]] (prominent).

Minor criteria:<ref name=pmid17213347/>
#Nuclear hyperchromasia.
#Wispy blue mucin.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f3.html#figure-title Wispy blue mucin (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Pink amorphous secretions.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html Pink amorphous secretions (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Intraluminal crystalloid.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f4.html#figure-title Intraluminal crystalloid (nature.com)] - from Epstein.<ref name=pmid14739905/>
#Amphophilic cytoplasm.
#*Amphopilic is said to be ''bluish-red''<ref>URL: [http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref> -- though might also be described as ''blue-grey''.
#**Image: [http://www.webpathology.com/image.asp?n=4&Case=20 Amphophilic cytoplasm is prostate carcinoma].
#Adjacent [[HGPIN]].
#Mitoses - quite rare.

Extent/quantity criteria:
*There is no agreed upon minimum number of glands; however, one paper suggests that agreement among experts is low with 5 or less glands.<ref name=pmid20061936>{{Cite journal | last1 = Van der Kwast | first1 = TH. | last2 = Evans | first2 = A. | last3 = Lockwood | first3 = G. | last4 = Tkachuk | first4 = D. | last5 = Bostwick | first5 = DG. | last6 = Epstein | first6 = JI. | last7 = Humphrey | first7 = PA. | last8 = Montironi | first8 = R. | last9 = Van Leenders | first9 = GJ. | title = Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 169-77 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c7997b | PMID = 20061936 }}</ref>
**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>

Features considered pathognomonic for prostate carcinoma by some authorities:<ref name=pmid16613324>{{Cite journal | last1 = Egevad | first1 = L. | last2 = Allsbrook | first2 = WC. | last3 = Epstein | first3 = JI. | title = Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists. | journal = Hum Pathol | volume = 37 | issue = 3 | pages = 292-7 | month = Mar | year = 2006 | doi = | PMID = 16613324 }}</ref><ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref>
#Perineural invasion.
#*Must be circumferential (>95% of circumference{{fact}}).
#Glomeruloid bodies.
#[[Collagenous micronodules]] also known as ''mucinous fibroplasia''.

<gallery>
Image: Intraluminal eosinophilic crystalloid of prostate gland - high mag.jpg| Intraluminal eosinophilic crystalloid - high mag. (WC)
Image: Prostate carcinoma with blue mucin -- very high mag.jpg | Whispy blue mucin - very high mag. (WC)
Image: Prostate carcinoma with blue mucin - a1 -- intermed mag.jpg | Whispy blue mucin - intermed. mag. (WC)
</gallery>

===Divided into high and low power===
====Low power features====
*Architecture is the '''key''' to diagnosing low grade cancer.
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Sharp transition between gland border and lumen.
***Loss of epithelial folding at the epithelium-gland lumen interface - "punched-out" appearance.
**Eosinophilic debris within the gland lumen (pink amorphous secretions, intraluminal crystalloid).
**Blue-tinged acellular material within the gland lumen (mucin) -- uncommon.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.

====High power features====
*Nuclear changes.
**Hyperchromatic nuclei (like in HGPIN).
**Nuclear enlargement, mild (10%?).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult/impossible to see at low power.
*"Large" nucleoli.
**Visible on intermediate and high power (100x / 200x magnification).
***May be difficult to see - especially if light intensity is low or the staining is of poor quality.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk over-calling something benign).
**"Large" is rarely precisely quantified; 3 micrometres has been suggested as "large" based on one study.<ref name=pmid1688728>{{Cite journal | last1 = Kelemen | first1 = PR. | last2 = Buschmann | first2 = RJ. | last3 = Weisz-Carrington | first3 = P. | title = Nucleolar prominence as a diagnostic variable in prostatic carcinoma. | journal = Cancer | volume = 65 | issue = 4 | pages = 1017-20 | month = Feb | year = 1990 | doi = | PMID = 1688728 }}</ref>
***Three micrometres is a little more than 1/3 of [[RBC]] diameter.
*Loss of basal cells - diagnostic feature.
**Like in [[breast pathology]] (where one looks for loss of myoepithelial cells) - this may be difficult to see.

Notes:
*Mitoses are not a common feature.
**If you find them the lesion is probably high-grade.
**Generally, it isn't worth looking for them.

===Mimics===
Mimics of prostate adenocarcinoma:<ref>{{Ref TPoSP|100-3}}</ref>
{| class="wikitable sortable"
! Entity
! Key feature
! Detailed microscopic
! Other
! Image
|-
| Adenosis ([[AKA]] ''atypical adenomatous hyperplasia'')
| gradual transition between normal & small gland (NOT two populations)
| many small glands, lack nuclear size variation, basal layer present
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| [[Image:Adenosis of prostate_--_intermed_mag.jpg|thumb|150px|center| Adenosis of prostate. (WC)]]
|-
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| analogous to [[sclerosing adenosis of the breast]]{{fact}}
| [http://webpathology.com/image.asp?case=21&n=40 Sclerosing adenosis (webpathology.com)]
|-
| [[atrophy of the prostate|Atrophy]]
| sharp angulation of gland
| nuclear hyperchromasia, scant cytoplasm
| may appear right beside non-atrophic tissue
| [[Image:Atrophic_prostatic_glands_--_high_mag.jpg|thumb|150px|center| Prostatic atrophy. (WC)]]
|-
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
| two distinct cell populations (in epithelial component)
| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| [[Image:Basal_cell_hyperplasia_of_prostate_-_high_mag.jpg|thumb|150px|center| Prostatic BCH. (WC)]]
|-
| [[Bulbourethral gland]]
| no nuclear atypia
| clear cytoplasm
| apex of prostate
| [[Image:Bulbourethral gland -- very high mag.jpg |thumb|150px|center| Bulbourethral gland. (WC)]]
|-
| [[Seminal vesicles]] / ejaculatory ducts
| lipofuscin (yellow granular material in cytoplasm), smudge cells (smeared appearance + hyperchromatic)
| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| [[Image:Seminal_vesicle_high_mag.jpg |thumb|150px|center|Seminal vesicles. (WC)]]
|-
| [[Radiation effect]]
| marked nuclear size variation
| increased stroma (fibrosis), lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of [[postradiation prostatic carcinoma|postradiation cancer]]
| [[Image:Prostate_with_radiation_changes_--_high_mag.jpg|thumb|150px|center|Radiation change. (WC)]]
|-
| Prostatitis
| inflammatory cells (lymphocytes, plasma cells, PMNs)
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| [[Image:Inflammation_of_prostate.jpg|thumb|150px|center| Prostatic inflammation. (WC)]]
|-
| [[Vasitis nodosa]]
| sperm within ducts, clinical history (usu. post-[[vasectomy]])
| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| [[Image:Vasitis nodosa -11- intermed mag.jpg|thumb|150px|center| VN. (WC)]]
|}
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.

===Situations where prostate adenocarcinoma may be missed<ref>{{cite journal |vauthors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}}</ref>===
*Tissue artefacts (try levels and/or IHC):
**Crush artefact
**Thick sections
**Aberrant H&E staining
**Freezing artefact
**Cautery
*Minimal adenocarcinoma (less than 1mm long or involving less than 5% of a core biopsy):
*Prostatic adenocarcinoma variants that mimic benign:
**[[Atrophic prostate carcinoma]]
**[[Pseudohyperplastic adenocarcinoma]]
**[[Foamy gland adenocarcinoma]]
**[[PIN-like adenocarcinoma]]
**Microcystic adenocarcinoma
*Single cells of Gleason 5 adenocarcinoma (missed or mistaken for lymphocytes; try IHC)
*Treatment effect (check clinical information and look for treatment effect in benign glands)

===Prostate cancer grading===
{{Main|Prostate cancer grading}}
It covers the ''Gleason grading system'' and the (new) ''prognostic grade groupings''.

===Staging parameters, margins and more===
====Surgical margins====
{{Main|Surgical margins}}
*Positive is ''tumour touching [[ink]]''.† <ref name=pmid22578729>{{Cite journal | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
**"Close" margins (<0.1 mm) have an increased recurrence risk.<ref name=pmid22578729/>

Notes:
*Surgical margin - where the surgeon cut.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
* † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.<ref>URL: [http://urology.jhu.edu/newsletter/prostate_cancer410.php http://urology.jhu.edu/newsletter/prostate_cancer410.php]. Accessed on: 26 March 2013.</ref>

=====Rates and implication=====
Positivity rate varies substantially (13-44%):
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*France: 13-17% -- PSA and prostate size predictors of positivity.<ref name=pmid22860572>{{Cite journal | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>

Note:
*Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.<ref name=pmid22860630/>

The impact of positive margins:
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Bladder neck margin positivity may change the T-stage - see below.

=====Bladder neck margin=====
{{Main|Bladder neck invasion}}
:[[AKA]] ''invasion of the bladder neck''.<ref name=pmid19914651/>
*Bladder neck margin positivity typically is '''pT3a'''.<ref name=pmid23225909>{{Cite journal | last1 = Chung | first1 = MS. | last2 = Lee | first2 = SH. | last3 = Lee | first3 = DH. | last4 = Chung | first4 = BH. | title = Evaluation of the 7th American Joint Committee on cancer TNM staging system for prostate cancer in point of classification of bladder neck invasion. | journal = Jpn J Clin Oncol | volume = 43 | issue = 2 | pages = 184-8 | month = Feb | year = 2013 | doi = 10.1093/jjco/hys196 | PMID = 23225909 }}</ref>
*Seen in approximately 1% of prostatectomies.<ref name=pmid19914651>{{Cite journal | last1 = Pierorazio | first1 = PM. | last2 = Epstein | first2 = JI. | last3 = Humphreys | first3 = E. | last4 = Han | first4 = M. | last5 = Walsh | first5 = PC. | last6 = Partin | first6 = AW. | title = The significance of a positive bladder neck margin after radical prostatectomy: the American Joint Committee on Cancer Pathological Stage T4 designation is not warranted. | journal = J Urol | volume = 183 | issue = 1 | pages = 151-7 | month = Jan | year = 2010 | doi = 10.1016/j.juro.2009.08.138 | PMID = 19914651 }}</ref>

====Extraprostatic extension====
:Abbreviated ''EPE''.
{{Main|Prostate cancer staging#Extraprostatic extension}}

====Seminal vesicle invasion====
:Abbreviated ''SVI''.
{{Main|Prostate cancer staging#Seminal vesicle invasion}}

====Perineural invasion====
{{Main|Perineural invasion}}
*''Not'' a staging parameter.
*Seen in approximately 20% of core biopsies.<ref name=pmid16096404>{{Cite journal | last1 = Ali | first1 = TZ. | last2 = Epstein | first2 = JI. | title = Perineural involvement by benign prostatic glands on needle biopsy. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1159-63 | month = Sep | year = 2005 | doi = | PMID = 16096404 }}</ref>
*Complete wrapping of a nerve by epithelium is considered pathognomonic for cancer.<ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref><ref name=pmid16096404/>

Note:
*Occasionally, benign glands are found perineural.<ref name=pmid16096404/>
**These should ''not'' completely wrap around the nerve and should be cytologically benign.

==IHC==
===General recommendations===
ISUP consensus statement:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*Should ''not'' be used if cancer is obvious.
*Should ''not'' be used if it isn't going change the clinical management.

===Prostate markers===
*[[PSA]] (prostate specific antigen) +ve.
*[[PSAP]] (prostatic specific acid phosphatase) +ve. †
*P501S +ve. ‡
*[[NKX3.1]] +ve. ‡

Notes:
*† PSAP may be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref>
*‡ P501S and NKX3.1 are considered second line markers.<ref name=pmid25025364/>
*Prostate carcinoma is typically CK7 -ve and CK20 -ve; however, in high [[Gleason score]] cancers focal positivity of these markers can be seen.<ref name=pmid11888088>{{Cite journal | last1 = Goldstein | first1 = NS. | title = Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. | journal = Am J Clin Pathol | volume = 117 | issue = 3 | pages = 471-7 | month = Mar | year = 2002 | doi = 10.1309/G6PR-Y774-X738-FG2K | PMID = 11888088 }}</ref>
**CK7: >25-50% staining seen in ~5% of cases.
***>50% staining with CK7 is not report.
**CK20: >25-50% staining seen in ~10% of cases.
***>50% staining with CK20 is not reported.

===Benign prostate versus neoplastic prostate===
*AMACR +ve.
*p63 -ve.
*HMWCK (34betaE12) -ve.

Combination immunostains:
*''PIN-4'' -- consists of: CK5 + CK14 + p63 + P504S (AMACR).<ref>URL: [http://biocare.net/wp-content/uploads/225DS.pdf http://biocare.net/wp-content/uploads/225DS.pdf]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/ http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.webpathology.com/image.asp?case=96&n=5 http://www.webpathology.com/image.asp?case=96&n=5]. Accessed on: 18 October 2011.</ref>
**[[AKA]] ''PIN''.
**[[AKA]] ''CAP''.
***Why '''CAP'''?
****A. '''CA'''ncer of the '''P'''rostate.

Other IHC stains:
*AR +ve -- in prostate confined cancer.
**Usually -ve in lymph node +ve disease.<ref name=pmid20878946>{{Cite journal | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>

Note:
*Bcl-2 marks basal cells in prostate cancer.<ref name=pmid20189848>{{Cite journal | last1 = Boran | first1 = C. | last2 = Kandirali | first2 = E. | last3 = Yilmaz | first3 = F. | last4 = Serin | first4 = E. | last5 = Akyol | first5 = M. | title = Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma. | journal = Urol Oncol | volume = 29 | issue = 6 | pages = 614-23 | month = | year = | doi = 10.1016/j.urolonc.2009.11.013 | PMID = 20189848 }}</ref>

====Prostate carcinoma versus urothelial carcinoma====
The ISUP panel recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*PSA +ve (-ve in UCC).
*GATA3 -ve (+ve in UCC).

Another panel - if GATA3 isn't available:
*Prostate: PSA +ve, p63 -ve, HWMCK -ve.
*Urothelial: p63 +ve, HWMCK +ve, PSA -ve.

Notes:
*AMACR not useful; it is positive in ~50% of [[UCC]].<ref name=pmid16315020>{{Cite journal | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*CK7 and CK20 are typically negative in prostate carcinoma, and classically positive in urothelial carcinoma.
*CK34betaE12 may be positive in prostate cancer; 43% of cases in one small series of cases with lymph node metastases.<ref name=pmid9024071>{{Cite journal | last1 = Googe | first1 = PB. | last2 = McGinley | first2 = KM. | last3 = Fitzgibbon | first3 = JF. | title = Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma. | journal = Am J Clin Pathol | volume = 107 | issue = 2 | pages = 219-23 | month = Feb | year = 1997 | doi = | PMID = 9024071 }}</ref>

===Rate of utilization===
*Dependent on practise setting.
**One tertiary academic institution uses it on ~ 40% of cases.<ref>{{Cite journal | last1 = Watson | first1 = K. | last2 = Wang | first2 = C. | last3 = Yilmaz | first3 = A. | last4 = Bismar | first4 = TA. | last5 = Trpkov | first5 = K. | title = Use of immunohistochemistry in routine workup of prostate needle biopsies: a tertiary academic institution experience. | journal = Arch Pathol Lab Med | volume = 137 | issue = 4 | pages = 541-5 | month = Apr | year = 2013 | doi = 10.5858/arpa.2012-0145-OA | PMID = 23273390 }}</ref>

==Molecular changes in prostate cancer==
A fusion gene between ''TMPRSS2'' and ''ERG'' is described.<ref name=pmid20478527>{{cite journal | author = Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM | title = An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression | journal = Cancer Cell | volume = 17 | issue = 5 | pages = 443–54 | year = 2010 | month = May | pmid = 20478527 | pmc = 2874722 | doi = 10.1016/j.ccr.2010.03.018 | url = }}</ref><ref name=omim602060>{{OMIM|602060}}</ref>
*Both genes are on chromosome 21.
*Currently ''not'' used diagnostically.
*Fusion gene seen in approximately 50% of prostate cancer.<ref name=omim602060>{{OMIM|602060}}</ref>
*A subset of ''TMPRSS2-ERG'' known as ''2+Edel'' (seen in ~7% of all prostate cancer cases) predicts poor survival.<ref name=pmid17637754>{{Cite journal | last1 = Attard | first1 = G. | last2 = Clark | first2 = J. | last3 = Ambroisine | first3 = L. | last4 = Fisher | first4 = G. | last5 = Kovacs | first5 = G. | last6 = Flohr | first6 = P. | last7 = Berney | first7 = D. | last8 = Foster | first8 = CS. | last9 = Fletcher | first9 = A. | title = Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. | journal = Oncogene | volume = 27 | issue = 3 | pages = 253-63 | month = Jan | year = 2008 | doi = 10.1038/sj.onc.1210640 | PMID = 17637754 }}</ref>

==Sign out==
===Prostatectomy specimens===
*A prostatectomy that appears to be negative should be worked-up. This is discuss in the ''[[negative prostatectomy]]'' article.
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP checklist].

<pre>
A. LYMPH NODES, RIGHT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

B. LYMPH NODES, LEFT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

C. PROSTATE GLAND AND SEMINAL VESICLES, RADICAL PROSTATECTOMY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4), pT2c pN0.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>

===Transurethral resection of prostate===
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 6/10 (3+3);
-- Approximately 2% of tissue involved;
-- Please see tumour summary.

Comment:
The World Health Organization (WHO) grade is: 1 out of 5.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 7/10 (3+4);
-- Approximately 4% of tissue involved;
-- Please see tumour summary.
- Benign inflamed urothelium.

Comment:
The World Health Organization (WHO) grade is: 2 out of 5. Gleason pattern 3 represents 90% of the tumour, and Gleason pattern 4 represents 10% of the tumour.
</pre>

====Block letters====
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.

TUMOUR SUMMARY - TRANSURETHRAL RESECTION OF PROSTATE (TURP).

PROCEDURE: TRANSURETHRAL PROSTATIC RESECTION.
SPECIMEN SIZE: WEIGHT: 10 GRAMS.
HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).

HISTOLOGIC GRADING:
PRIMARY PATTERN: 3.
SECONDARY PATTERN: 4 (40% OF TUMOUR).
TOTAL GLEASON SCORE: 7 (3+4).

TUMOUR QUANTITATION - PERCENTAGE OF PROSTATIC TISSUE INVOLVED BY TUMOUR: 80 %.

PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
SEMINAL VESICLE INVASION: NOT IDENTIFIED.
LYMPH-VASCULAR INVASION: NOT IDENTIFIED.
PERINEURAL INVASION: NOT IDENTIFIED.

ADDITIONAL PATHOLOGIC FINDINGS:
HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).
NODULAR PROSTATIC HYPERPLASIA.
CHRONIC INFLAMMATION.
</pre>

<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- Adenocarcinoma, Gleason score 7 (3+4)
- Approximately 3% of sampled tissue involved
- Please see tumour summary

Tumour summary:
Procedure: Transurethral resection of prostate
Specimen weight: 11.7 g
Histologic type: Adenocarcinoma, acinar type

Histologic grade:
Primary pattern: 3
Secondary pattern: 4 (<15% of tumor)
Total Gleason score: 7/10 (3+4)

Tumor volume: 3% of tissue

Periprostate fat invasion: Periprostatic fat not identified
Seminal vesicle invasion: Seminal vesicle not identified
Lymphovascular inasion: Not identified
Perineural invasion: Not identified

Additional findings:
Glandular and stromal hyperplasia
Mild chronic inflammation
</pre>

===Biopsy specimens===
Important elements - a list:<ref name=pmid17213347/>
#Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
#Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
#Number of cores and number involved, e.g. "2/3 cores involved by cancer".
#Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour". ‡
#Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
#Presence of [[perineural invasion]].
#Presence of extension into fat (extraprostatic extension).

Notes:
*‡ "Percent area involved" may seem like an odd thing to request 'cause it is sampling dependent, i.e. if the radiologist sticks the biopsy needle deeper into the lesion more of the core is positive, but urologists think it is important -- more important than perineural invasion.<ref name=pmid15223967>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.<ref name=pmid22688447>{{Cite journal | last1 = Fu | first1 = Q. | last2 = Moul | first2 = JW. | last3 = Bañez | first3 = LL. | last4 = Sun | first4 = L. | last5 = Mouraviev | first5 = V. | last6 = Xie | first6 = D. | last7 = Polascik | first7 = TJ. | title = Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer. | journal = Med Oncol | volume = 29 | issue = 5 | pages = 3339-44 | month = Dec | year = 2012 | doi = 10.1007/s12032-012-0270-4 | PMID = 22688447 }}</ref>

====Completely negative====
<pre>
A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

C. PROSTATE, RIGHT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

D. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

E. PROSTATE, RIGHT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

I. PROSTATE, LEFT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

J. PROSTATE, LEFT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

K. PROSTATE, LEFT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
</pre>

====Negative biopsy in surveillance====
<pre>
COMMENT:
The previous results are noted. The absence of cancer in this biopsy may
be due to sampling.
</pre>

====No glands====
<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN FIBROMUSCULAR TISSUE;
- NO PROSTATIC GLANDULAR TISSUE PRESENT.
</pre>

====Inflammation====
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- ACUTE AND CHRONIC INFLAMMATION.
</pre>

====Positive====
<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 25% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

=====Tumour summaries=====
*These are not completely without controversy.
*It should be noted that treatment is driven by the highest Gleason score.{{fact}}

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- TOTAL GLEASON SCORE: 7.
- PRIMARY PATTERN: 4.
- SECONDARY PATTERN: 3.
- PERCENT OF TUMOUR WITH PATTERN HIGHER THAN GRADE 3: 75%.

- NUMBER OF CORES POSITIVE: 10.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 152 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 44%.

- PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: SEMINAL VESICLE NOT IDENTIFIED.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- PERINEURAL INVASION: PRESENT.

- ADDITIONAL FINDINGS: HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA, CHRONIC INFLAMMATION (FOCAL).
</pre>

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- HIGHEST GLEASON SCORE: 8 (4+4).
- SUMMARY GLEASON SCORE: 7 (4+3).
- PERCENT OF TUMOUR WITH PATTERN 4: 55%.
- PERCENT OF TUMOUR WITH PATTERN 5: 0%.

- NUMBER OF CORES POSITIVE: 12.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 178 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 80%.

- PERINEURAL INVASION: PRESENT.
- PERIPROSTATIC FAT INVASION: PRESENT.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: NOT IDENTIFIED.
</pre>

===Seminal vesicle/ejaculatory duct invasion on biopsy===
<pre>
COMMENT:
The seminal vesicles and ejaculatory ducts have the same histology; thus, it is not
usually possible to confidently differentiate them in a needle biopsy.

SV/ED invasion was demonstrated with CK7, CK34betaE12/AMACR, PSA and p63 immunostaining.
The tumour is PSA and AMACR positive.
</pre>

=Intraductal spread of prostate cancer=
==Intraductal carcinoma of the prostate==
*[[AKA]] ''[[intraductal carcinoma]]''.
*[[AKA]] ''intraductal prostate carcinoma''.
{{Main|Intraductal carcinoma of the prostate}}

=Unusual forms of prostate cancer=
==Prostatic ductal adenocarcinoma==
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
{{Main|Ductal adenocarcinoma of the prostate gland}}

==PIN-like prostatic ductal adenocarcinoma==
{{Main|High-grade prostatic intraepithelial neoplasia-like ductal adenocarcinoma of the prostate}}

==Foamy gland carcinoma==
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862>{{Cite journal | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
{{Main|Foamy gland carcinoma}}

==Atrophic prostate carcinoma==
*[[AKA]] ''atrophic carcinoma''.
{{Main|Atrophic prostate carcinoma}}

==Mucinous prostate carcinoma==
{{Main|Mucinous adenocarcinoma of the prostate}}

==Pseudohyperplastic prostatic adenocarcinoma==
*[[AKA]] ''pseudohyperplastic adenocarcinoma''.
{{Main|Pseudohyperplastic prostatic adenocarcinoma}}

==Prostatic signet ring cell carcinoma==
{{Main|Signet ring cell carcinoma}}
===General===
*Very rare - 9 cases in a series of 29,783 prostate cancer cases.<ref name=pmid21123640>{{Cite journal | last1 = Warner | first1 = JN. | last2 = Nakamura | first2 = LY. | last3 = Pacelli | first3 = A. | last4 = Humphreys | first4 = MR. | last5 = Castle | first5 = EP. | title = Primary signet ring cell carcinoma of the prostate. | journal = Mayo Clin Proc | volume = 85 | issue = 12 | pages = 1130-6 | month = Dec | year = 2010 | doi = 10.4065/mcp.2010.0463 | PMID = 21123640 }}</ref>
*Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.<ref name=pmid21123640/>

===Microscopic===
Features:
*Signet ring cells - see ''[[basics]]'' article.

DDx:
*Acinar adenocarcinoma - Gleason pattern 4 with very small glands.

====Images====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRCC (nih.gov)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f7.html#figure-title Prostatic SRCC (nature.com)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f8.html Prostatic SRCC (nature.com)].
*[http://www.webpathology.com/image.asp?case=23&n=34 Prostatic SRCC (webpathology.com)] - looks like ''acinar adenocarcinoma''.

===Stains===
*Alcian blue-PAS stain +ve.
*[[PAS stain|PAS]] -- 50% of cases +ve.<ref name=pmid21123640/>
*[[Alcian blue stain|Alcian blue]] -- 44% of cases +ve.<ref name=pmid21123640/>

==Sarcomatoid carcinoma of the prostate==
{{Main|Sarcomatoid carcinoma of the prostate}}

==Small cell carcinoma of the prostate gland==
{{Main|Small cell carcinoma of the prostate gland}}

==Adenoid cystic/basal cell carcinoma of the prostate==
*Abbreviated ''ACBCC''.
{{Main|Adenoid cystic/basal cell carcinoma of the prostate}}

==Postradiation prostate cancer==
{{Main|Postradiation prostate cancer}}

=Metastatic disease and other cancers of the prostate=
==Urothelial carcinoma==
{{Main|Urothelial carcinoma of the urethra}}

=See also=
*[[Prostate gland]].
*[[Genitourinary pathology]]

=References=
{{Reflist|2}}

[[Category:Genitourinary pathology]]
[[Category:Prostate carcinoma]]

Prostate cancer

2020-03-05T15:37:12Z

{{ Infobox diagnosis
| Name = Prostate carcinoma
| Image = Prostate cancer with Gleason pattern 4 low mag.jpg
| Width =
| Caption = Prostate carcinoma. [[H&E stain]].
| Micro = major criteria: abnormal architecture (increased gland density, usu. small circular glands, "infiltrative growth" pattern), basal cells lost, cytological abnormalities (nuclear enlargement, nucleoli); minor criteria: nuclear hyperchromasia, wispy blue mucin, pink amorphous secretions, intraluminal crystalloid, amphophilic cytoplasm, adjacent [[HGPIN]], mitoses
| Subtypes =
| LMDDx = [[high-grade prostatic intraepithelial neoplasia]], [[atypical small acinar proliferation]] (biopsy only), [[prostatic atrophy]], [[seminal vesicle]], [[basal cell hyperplasia of the prostate|basal cell hyperplasia]], others
| Stains =
| IHC = PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
| EM =
| Molecular = +/-[[BRCA1]] mutation (genetic predisposition), +/-[[BRCA2]] mutation (genetic predisposition)
| IF =
| Gross = usu. posterior aspect of the prostate - often not apparent at gross
| Grossing = [[prostate biopsy]], [[prostate chips]], [[radical prostatectomy]]
| Staging = [[prostate cancer staging]]
| Site = [[prostate gland]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs = firm, nodular prostate on digital rectal exam
| Symptoms = often asymptomatic
| Prevalence = very common
| Bloodwork = PSA elevated (common)
| Rads = hypoechoic areas, no apparent abnormality
| Endoscopy =
| Prognosis = good-to-poor (depends on [[prostate cancer grading|grade (Gleason score)]] and [[stage]])
| Other =
| ClinDDx = [[prostatitis]], [[nodular hyperplasia of the prostate]]
| Tx = observation (common for low-grade, low tumour burden), radiation or radical prostatectomy
}}
This article deals with '''prostate [[cancer]]'''.

The vast majority of prostate cancers are carcinomas and could be labelled '''prostatic carcinoma'''. Most prostatic carcinomas are gland forming; thus, they can be labelled '''prostatic [[adenocarcinoma]]''' or '''adenocarcinoma of the prostate'''.

Benign pathology of the prostate gland, and prostate histology and anatomy are dealt with in the ''[[prostate gland]]'' article.

=Conventional prostate cancer=
==General==
*Very common.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.<ref>{{cite journal |author=Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD |title=The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients |journal=J. Urol. |volume=150 |issue=2 Pt 1 |pages=379–85 |year=1993 |month=August |pmid=8326560 |doi= |url=}}</ref>{{fact}}
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.

*Risk increased with a [[BRCA1]] or [[BRCA2]] mutation<ref name=pmid23747895>{{Cite journal | last1 = Li | first1 = D. | last2 = Kumaraswamy | first2 = E. | last3 = Harlan-Williams | first3 = LM. | last4 = Jensen | first4 = RA. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Front Biosci (Landmark Ed) | volume = 18 | issue = | pages = 1445-59 | month = | year = 2013 | doi = | PMID = 23747895 }}</ref> - families have a mix of [[breast cancer]] and prostate cancer.
**BRCA2 mutation risk >8x for men over 65 years old.<ref name=pmid22522501>{{Cite journal | last1 = Castro | first1 = E. | last2 = Eeles | first2 = R. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Asian J Androl | volume = 14 | issue = 3 | pages = 409-14 | month = May | year = 2012 | doi = 10.1038/aja.2011.150 | PMID = 22522501 }}</ref>
**A BRCA2 founder mutation is described in French Canadians.<Ref name=pmid23318356>{{Cite journal | last1 = Taherian | first1 = N. | last2 = Hamel | first2 = N. | last3 = Bégin | first3 = LR. | last4 = Bismar | first4 = TA. | last5 = Goldgar | first5 = DE. | last6 = Feng | first6 = BJ. | last7 = Foulkes | first7 = WD. | title = Familial prostate cancer: the damage done and lessons learnt. | journal = Nat Rev Urol | volume = 10 | issue = 2 | pages = 116-22 | month = Feb | year = 2013 | doi = 10.1038/nrurol.2012.257 | PMID = 23318356 }}</ref>

===Management===
====Dirty first approximation====
*The management changes between [[Gleason score]] 6, 7 (3+4), 7 (4+3) and 8.

Typically, the implications are:
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 7 with a bit of Gleason pattern 4 and a low tumour volume: it is reasonable to watch ''or'' do something. ‡
* Gleason 7 with a lot of Gleason pattern 4 ''or'' a high tumour volume: do something -- surgery ''or'' radiation therapy.
* Gleason 8+: bad cancer -- do something quickly!

Note:
* ‡ It has been said that ''Gleason score 7 with a bit of Gleason pattern 4 is the new Gleason score 6''.

Bottom line:
*You want to be sure when you call something Gleason pattern 4.

====Observational strategies====
*Delay of definitive treatment (surgery ''or'' radiation).
*Common in the management of prostate cancer.

Classification:<ref name=pmid23126653>{{Cite journal | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume = | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi = | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
*Active surveillance (AS).
**Low risk of progression.
**May get definitive treatment later.
*Watchful waiting (WW).
**Higher risk of progression.

Note:
*There is no agreed upon set of criteria for active surveillance, and the large number of criteria out there vary significantly.<ref name=pmid22314081>{{Cite journal | last1 = Palisaar | first1 = JR. | last2 = Noldus | first2 = J. | last3 = Löppenberg | first3 = B. | last4 = von Bodman | first4 = C. | last5 = Sommerer | first5 = F. | last6 = Eggert | first6 = T. | title = Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. | journal = BJU Int | volume = 110 | issue = 6 Pt B | pages = E172-81 | month = Sep | year = 2012 | doi = 10.1111/j.1464-410X.2012.10935.x | PMID = 22314081 }}</ref>

=====Active surveillance=====
The ''Klotz'' criteria for active surveillance - pathologic factors only:<ref name=pmid22314081/><ref>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for prostate cancer: for whom? | journal = J Clin Oncol | volume = 23 | issue = 32 | pages = 8165-9 | month = Nov | year = 2005 | doi = 10.1200/JCO.2005.03.3134 | PMID = 16278468 }}</ref>
*Gleason score 6 or less.
*All biopsies cores < 50% involvement.
*One or two cores involved.<ref>URL: [http://www.active-surveillance.com/laurence-klotz-md/ http://www.active-surveillance.com/laurence-klotz-md/]. Accessed on: 12 July 2013.</ref><ref name=pmid23548978>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance: patient selection. | journal = Curr Opin Urol | volume = 23 | issue = 3 | pages = 239-44 | month = May | year = 2013 | doi = 10.1097/MOU.0b013e32835f8f6b | PMID = 23548978 }}</ref><ref name=pmid22891078>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for low-risk prostate cancer. | journal = F1000 Med Rep | volume = 4 | issue = | pages = 16 | month = | year = 2012 | doi = 10.3410/M4-16 | PMID = 22891078 | PMC = 3412317 }}</ref>
Clinical criteria:
*PSA <= 10 ng/mL.<ref name=pmid22314081/>
*Negative DRE.

==Gross==
*Prostate cancer is uncommonly apparent on gross.
*Classic location: posterior aspect of the prostate.

===Radiology===
*Hypoechoic areas = suspicious for cancer.
**It seems that size of the area matters.
***Small hypoechoic areas (<0.2 cm3) have cancer less than 4% of the time.<ref name=pmid9933054>{{Cite journal | last1 = Fleshner | first1 = NE. | last2 = O'Sullivan | first2 = M. | last3 = Premdass | first3 = C. | last4 = Fair | first4 = WR. | title = Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL. | journal = Urology | volume = 53 | issue = 2 | pages = 356-8 | month = Feb | year = 1999 | doi = | PMID = 9933054 }}</ref>
***One study suggests hypoechoic lesions tend to have a worse outcome;<ref name=pmid22920545>{{Cite journal | last1 = Nakano Junqueira | first1 = VC. | last2 = Zogbi | first2 = O. | last3 = Cologna | first3 = A. | last4 = Dos Reis | first4 = RB. | last5 = Tucci | first5 = S. | last6 = Reis | first6 = LO. | last7 = Westphalen | first7 = AC. | last8 = Muglia | first8 = VF. | title = Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? | journal = Ultrasound Med Biol | volume = 38 | issue = 10 | pages = 1689-94 | month = Oct | year = 2012 | doi = 10.1016/j.ultrasmedbio.2012.06.006 | PMID = 22920545 }}</ref> however, this is not supported by an older study.<ref name=pmid1688955>{{Cite journal | last1 = Devonec | first1 = M. | last2 = Fendler | first2 = JP. | last3 = Monsallier | first3 = M. | last4 = Mouriquand | first4 = P. | last5 = Maquet | first5 = JH. | last6 = Mestas | first6 = JL. | last7 = Dutrieux-Berger | first7 = N. | last8 = Perrin | first8 = P. | title = The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. | journal = J Urol | volume = 143 | issue = 2 | pages = 316-9 | month = Feb | year = 1990 | doi = | PMID = 1688955 }}</ref>

===Prostatectomy grossing===
{{Main|Radical prostatectomy}}

===Cytoprostatectomy grossing===
{{Main|Cystoprostatectomy grossing}}
*Limited sampling of the prostate may lead to undersampling error.<ref name=pmid11182038>{{Cite journal | last1 = Cindolo | first1 = L. | last2 = Benincasa | first2 = G. | last3 = Autorino | first3 = R. | last4 = Domizio | first4 = S. | last5 = De Rosa | first5 = G. | last6 = Testa | first6 = G. | last7 = D'Armiento | first7 = M. | last8 = Altieri | first8 = V. | title = Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study. | journal = Oncol Rep | volume = 8 | issue = 2 | pages = 269-71 | month = | year = | doi = | PMID = 11182038 }}</ref>

==Microscopic==
===Criteria as a list===
Major criteria (the ABCs of prostate pathology):<ref name=pmid17213347>{{cite journal |author=Humphrey PA |title=Diagnosis of adenocarcinoma in prostate needle biopsy tissue |journal=J. Clin. Pathol. |volume=60 |issue=1 |pages=35–42 |year=2007 |month=January |pmid=17213347 |pmc=1860598 |doi=10.1136/jcp.2005.036442 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed}}</ref>
#Architecture.
#*Increased gland density.
#*Small circular glands.
#**In rare subtypes - large branching glands.
#*"Infiltrative growth" pattern - malignant glands between benign ones.
#**Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f1.html#figure-title Infiltrative growth pattern (nature.com)].
#Basal cells lacking.
#Cytological abnormalities:
#*Nuclear enlargement (subtle).
#*[[Nucleoli]] (prominent).

Minor criteria:<ref name=pmid17213347/>
#Nuclear hyperchromasia.
#Wispy blue mucin.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f3.html#figure-title Wispy blue mucin (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Pink amorphous secretions.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html Pink amorphous secretions (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Intraluminal crystalloid.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f4.html#figure-title Intraluminal crystalloid (nature.com)] - from Epstein.<ref name=pmid14739905/>
#Amphophilic cytoplasm.
#*Amphopilic is said to be ''bluish-red''<ref>URL: [http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref> -- though might also be described as ''blue-grey''.
#**Image: [http://www.webpathology.com/image.asp?n=4&Case=20 Amphophilic cytoplasm is prostate carcinoma].
#Adjacent [[HGPIN]].
#Mitoses - quite rare.

Extent/quantity criteria:
*There is no agreed upon minimum number of glands; however, one paper suggests that agreement among experts is low with 5 or less glands.<ref name=pmid20061936>{{Cite journal | last1 = Van der Kwast | first1 = TH. | last2 = Evans | first2 = A. | last3 = Lockwood | first3 = G. | last4 = Tkachuk | first4 = D. | last5 = Bostwick | first5 = DG. | last6 = Epstein | first6 = JI. | last7 = Humphrey | first7 = PA. | last8 = Montironi | first8 = R. | last9 = Van Leenders | first9 = GJ. | title = Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 169-77 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c7997b | PMID = 20061936 }}</ref>
**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>

Features considered pathognomonic for prostate carcinoma by some authorities:<ref name=pmid16613324>{{Cite journal | last1 = Egevad | first1 = L. | last2 = Allsbrook | first2 = WC. | last3 = Epstein | first3 = JI. | title = Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists. | journal = Hum Pathol | volume = 37 | issue = 3 | pages = 292-7 | month = Mar | year = 2006 | doi = | PMID = 16613324 }}</ref><ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref>
#Perineural invasion.
#*Must be circumferential (>95% of circumference{{fact}}).
#Glomeruloid bodies.
#[[Collagenous micronodules]] also known as ''mucinous fibroplasia''.

<gallery>
Image: Intraluminal eosinophilic crystalloid of prostate gland - high mag.jpg| Intraluminal eosinophilic crystalloid - high mag. (WC)
Image: Prostate carcinoma with blue mucin -- very high mag.jpg | Whispy blue mucin - very high mag. (WC)
Image: Prostate carcinoma with blue mucin - a1 -- intermed mag.jpg | Whispy blue mucin - intermed. mag. (WC)
</gallery>

===Divided into high and low power===
====Low power features====
*Architecture is the '''key''' to diagnosing low grade cancer.
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Sharp transition between gland border and lumen.
***Loss of epithelial folding at the epithelium-gland lumen interface - "punched-out" appearance.
**Eosinophilic debris within the gland lumen (pink amorphous secretions, intraluminal crystalloid).
**Blue-tinged acellular material within the gland lumen (mucin) -- uncommon.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.

====High power features====
*Nuclear changes.
**Hyperchromatic nuclei (like in HGPIN).
**Nuclear enlargement, mild (10%?).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult/impossible to see at low power.
*"Large" nucleoli.
**Visible on intermediate and high power (100x / 200x magnification).
***May be difficult to see - especially if light intensity is low or the staining is of poor quality.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk over-calling something benign).
**"Large" is rarely precisely quantified; 3 micrometres has been suggested as "large" based on one study.<ref name=pmid1688728>{{Cite journal | last1 = Kelemen | first1 = PR. | last2 = Buschmann | first2 = RJ. | last3 = Weisz-Carrington | first3 = P. | title = Nucleolar prominence as a diagnostic variable in prostatic carcinoma. | journal = Cancer | volume = 65 | issue = 4 | pages = 1017-20 | month = Feb | year = 1990 | doi = | PMID = 1688728 }}</ref>
***Three micrometres is a little more than 1/3 of [[RBC]] diameter.
*Loss of basal cells - diagnostic feature.
**Like in [[breast pathology]] (where one looks for loss of myoepithelial cells) - this may be difficult to see.

Notes:
*Mitoses are not a common feature.
**If you find them the lesion is probably high-grade.
**Generally, it isn't worth looking for them.

===Mimics===
Mimics of prostate adenocarcinoma:<ref>{{Ref TPoSP|100-3}}</ref>
{| class="wikitable sortable"
! Entity
! Key feature
! Detailed microscopic
! Other
! Image
|-
| Adenosis ([[AKA]] ''atypical adenomatous hyperplasia'')
| gradual transition between normal & small gland (NOT two populations)
| many small glands, lack nuclear size variation, basal layer present
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| [[Image:Adenosis of prostate_--_intermed_mag.jpg|thumb|150px|center| Adenosis of prostate. (WC)]]
|-
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| analogous to [[sclerosing adenosis of the breast]]{{fact}}
| [http://webpathology.com/image.asp?case=21&n=40 Sclerosing adenosis (webpathology.com)]
|-
| [[atrophy of the prostate|Atrophy]]
| sharp angulation of gland
| nuclear hyperchromasia, scant cytoplasm
| may appear right beside non-atrophic tissue
| [[Image:Atrophic_prostatic_glands_--_high_mag.jpg|thumb|150px|center| Prostatic atrophy. (WC)]]
|-
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
| two distinct cell populations (in epithelial component)
| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| [[Image:Basal_cell_hyperplasia_of_prostate_-_high_mag.jpg|thumb|150px|center| Prostatic BCH. (WC)]]
|-
| [[Bulbourethral gland]]
| no nuclear atypia
| clear cytoplasm
| apex of prostate
| [[Image:Bulbourethral gland -- very high mag.jpg |thumb|150px|center| Bulbourethral gland. (WC)]]
|-
| [[Seminal vesicles]] / ejaculatory ducts
| lipofuscin (yellow granular material in cytoplasm), smudge cells (smeared appearance + hyperchromatic)
| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| [[Image:Seminal_vesicle_high_mag.jpg |thumb|150px|center|Seminal vesicles. (WC)]]
|-
| [[Radiation effect]]
| marked nuclear size variation
| increased stroma (fibrosis), lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of [[postradiation prostatic carcinoma|postradiation cancer]]
| [[Image:Prostate_with_radiation_changes_--_high_mag.jpg|thumb|150px|center|Radiation change. (WC)]]
|-
| Prostatitis
| inflammatory cells (lymphocytes, plasma cells, PMNs)
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| [[Image:Inflammation_of_prostate.jpg|thumb|150px|center| Prostatic inflammation. (WC)]]
|-
| [[Vasitis nodosa]]
| sperm within ducts, clinical history (usu. post-[[vasectomy]])
| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| [[Image:Vasitis nodosa -11- intermed mag.jpg|thumb|150px|center| VN. (WC)]]
|}
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.

===Situations where prostate adenocarcinoma may be missed<ref>{{cite journal |vauthors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}}</ref>===
*Tissue artefacts (try levels and/or IHC)
**Crush artefact obscuring architectural or cytologic features
**Thick section
**Aberration in H&E staining obscuring cytologic features
**Freezing artefact
*Minimal adenocarcinoma
*Prostatic adenocarcinoma variants that mimic benign:
**[[Atrophic prostate carcinoma]].
**[[Pseudohyperplastic adenocarcinoma]].
**[[Foamy gland adenocarcinoma]].
**[[PIN-like adenocarcinoma]].
*Single-cell adenocarcinoma
*Treatment effect

===Prostate cancer grading===
{{Main|Prostate cancer grading}}
It covers the ''Gleason grading system'' and the (new) ''prognostic grade groupings''.

===Staging parameters, margins and more===
====Surgical margins====
{{Main|Surgical margins}}
*Positive is ''tumour touching [[ink]]''.† <ref name=pmid22578729>{{Cite journal | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
**"Close" margins (<0.1 mm) have an increased recurrence risk.<ref name=pmid22578729/>

Notes:
*Surgical margin - where the surgeon cut.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
* † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.<ref>URL: [http://urology.jhu.edu/newsletter/prostate_cancer410.php http://urology.jhu.edu/newsletter/prostate_cancer410.php]. Accessed on: 26 March 2013.</ref>

=====Rates and implication=====
Positivity rate varies substantially (13-44%):
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*France: 13-17% -- PSA and prostate size predictors of positivity.<ref name=pmid22860572>{{Cite journal | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>

Note:
*Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.<ref name=pmid22860630/>

The impact of positive margins:
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Bladder neck margin positivity may change the T-stage - see below.

=====Bladder neck margin=====
{{Main|Bladder neck invasion}}
:[[AKA]] ''invasion of the bladder neck''.<ref name=pmid19914651/>
*Bladder neck margin positivity typically is '''pT3a'''.<ref name=pmid23225909>{{Cite journal | last1 = Chung | first1 = MS. | last2 = Lee | first2 = SH. | last3 = Lee | first3 = DH. | last4 = Chung | first4 = BH. | title = Evaluation of the 7th American Joint Committee on cancer TNM staging system for prostate cancer in point of classification of bladder neck invasion. | journal = Jpn J Clin Oncol | volume = 43 | issue = 2 | pages = 184-8 | month = Feb | year = 2013 | doi = 10.1093/jjco/hys196 | PMID = 23225909 }}</ref>
*Seen in approximately 1% of prostatectomies.<ref name=pmid19914651>{{Cite journal | last1 = Pierorazio | first1 = PM. | last2 = Epstein | first2 = JI. | last3 = Humphreys | first3 = E. | last4 = Han | first4 = M. | last5 = Walsh | first5 = PC. | last6 = Partin | first6 = AW. | title = The significance of a positive bladder neck margin after radical prostatectomy: the American Joint Committee on Cancer Pathological Stage T4 designation is not warranted. | journal = J Urol | volume = 183 | issue = 1 | pages = 151-7 | month = Jan | year = 2010 | doi = 10.1016/j.juro.2009.08.138 | PMID = 19914651 }}</ref>

====Extraprostatic extension====
:Abbreviated ''EPE''.
{{Main|Prostate cancer staging#Extraprostatic extension}}

====Seminal vesicle invasion====
:Abbreviated ''SVI''.
{{Main|Prostate cancer staging#Seminal vesicle invasion}}

====Perineural invasion====
{{Main|Perineural invasion}}
*''Not'' a staging parameter.
*Seen in approximately 20% of core biopsies.<ref name=pmid16096404>{{Cite journal | last1 = Ali | first1 = TZ. | last2 = Epstein | first2 = JI. | title = Perineural involvement by benign prostatic glands on needle biopsy. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1159-63 | month = Sep | year = 2005 | doi = | PMID = 16096404 }}</ref>
*Complete wrapping of a nerve by epithelium is considered pathognomonic for cancer.<ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref><ref name=pmid16096404/>

Note:
*Occasionally, benign glands are found perineural.<ref name=pmid16096404/>
**These should ''not'' completely wrap around the nerve and should be cytologically benign.

==IHC==
===General recommendations===
ISUP consensus statement:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*Should ''not'' be used if cancer is obvious.
*Should ''not'' be used if it isn't going change the clinical management.

===Prostate markers===
*[[PSA]] (prostate specific antigen) +ve.
*[[PSAP]] (prostatic specific acid phosphatase) +ve. †
*P501S +ve. ‡
*[[NKX3.1]] +ve. ‡

Notes:
*† PSAP may be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref>
*‡ P501S and NKX3.1 are considered second line markers.<ref name=pmid25025364/>
*Prostate carcinoma is typically CK7 -ve and CK20 -ve; however, in high [[Gleason score]] cancers focal positivity of these markers can be seen.<ref name=pmid11888088>{{Cite journal | last1 = Goldstein | first1 = NS. | title = Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. | journal = Am J Clin Pathol | volume = 117 | issue = 3 | pages = 471-7 | month = Mar | year = 2002 | doi = 10.1309/G6PR-Y774-X738-FG2K | PMID = 11888088 }}</ref>
**CK7: >25-50% staining seen in ~5% of cases.
***>50% staining with CK7 is not report.
**CK20: >25-50% staining seen in ~10% of cases.
***>50% staining with CK20 is not reported.

===Benign prostate versus neoplastic prostate===
*AMACR +ve.
*p63 -ve.
*HMWCK (34betaE12) -ve.

Combination immunostains:
*''PIN-4'' -- consists of: CK5 + CK14 + p63 + P504S (AMACR).<ref>URL: [http://biocare.net/wp-content/uploads/225DS.pdf http://biocare.net/wp-content/uploads/225DS.pdf]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/ http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.webpathology.com/image.asp?case=96&n=5 http://www.webpathology.com/image.asp?case=96&n=5]. Accessed on: 18 October 2011.</ref>
**[[AKA]] ''PIN''.
**[[AKA]] ''CAP''.
***Why '''CAP'''?
****A. '''CA'''ncer of the '''P'''rostate.

Other IHC stains:
*AR +ve -- in prostate confined cancer.
**Usually -ve in lymph node +ve disease.<ref name=pmid20878946>{{Cite journal | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>

Note:
*Bcl-2 marks basal cells in prostate cancer.<ref name=pmid20189848>{{Cite journal | last1 = Boran | first1 = C. | last2 = Kandirali | first2 = E. | last3 = Yilmaz | first3 = F. | last4 = Serin | first4 = E. | last5 = Akyol | first5 = M. | title = Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma. | journal = Urol Oncol | volume = 29 | issue = 6 | pages = 614-23 | month = | year = | doi = 10.1016/j.urolonc.2009.11.013 | PMID = 20189848 }}</ref>

====Prostate carcinoma versus urothelial carcinoma====
The ISUP panel recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*PSA +ve (-ve in UCC).
*GATA3 -ve (+ve in UCC).

Another panel - if GATA3 isn't available:
*Prostate: PSA +ve, p63 -ve, HWMCK -ve.
*Urothelial: p63 +ve, HWMCK +ve, PSA -ve.

Notes:
*AMACR not useful; it is positive in ~50% of [[UCC]].<ref name=pmid16315020>{{Cite journal | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*CK7 and CK20 are typically negative in prostate carcinoma, and classically positive in urothelial carcinoma.
*CK34betaE12 may be positive in prostate cancer; 43% of cases in one small series of cases with lymph node metastases.<ref name=pmid9024071>{{Cite journal | last1 = Googe | first1 = PB. | last2 = McGinley | first2 = KM. | last3 = Fitzgibbon | first3 = JF. | title = Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma. | journal = Am J Clin Pathol | volume = 107 | issue = 2 | pages = 219-23 | month = Feb | year = 1997 | doi = | PMID = 9024071 }}</ref>

===Rate of utilization===
*Dependent on practise setting.
**One tertiary academic institution uses it on ~ 40% of cases.<ref>{{Cite journal | last1 = Watson | first1 = K. | last2 = Wang | first2 = C. | last3 = Yilmaz | first3 = A. | last4 = Bismar | first4 = TA. | last5 = Trpkov | first5 = K. | title = Use of immunohistochemistry in routine workup of prostate needle biopsies: a tertiary academic institution experience. | journal = Arch Pathol Lab Med | volume = 137 | issue = 4 | pages = 541-5 | month = Apr | year = 2013 | doi = 10.5858/arpa.2012-0145-OA | PMID = 23273390 }}</ref>

==Molecular changes in prostate cancer==
A fusion gene between ''TMPRSS2'' and ''ERG'' is described.<ref name=pmid20478527>{{cite journal | author = Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM | title = An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression | journal = Cancer Cell | volume = 17 | issue = 5 | pages = 443–54 | year = 2010 | month = May | pmid = 20478527 | pmc = 2874722 | doi = 10.1016/j.ccr.2010.03.018 | url = }}</ref><ref name=omim602060>{{OMIM|602060}}</ref>
*Both genes are on chromosome 21.
*Currently ''not'' used diagnostically.
*Fusion gene seen in approximately 50% of prostate cancer.<ref name=omim602060>{{OMIM|602060}}</ref>
*A subset of ''TMPRSS2-ERG'' known as ''2+Edel'' (seen in ~7% of all prostate cancer cases) predicts poor survival.<ref name=pmid17637754>{{Cite journal | last1 = Attard | first1 = G. | last2 = Clark | first2 = J. | last3 = Ambroisine | first3 = L. | last4 = Fisher | first4 = G. | last5 = Kovacs | first5 = G. | last6 = Flohr | first6 = P. | last7 = Berney | first7 = D. | last8 = Foster | first8 = CS. | last9 = Fletcher | first9 = A. | title = Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. | journal = Oncogene | volume = 27 | issue = 3 | pages = 253-63 | month = Jan | year = 2008 | doi = 10.1038/sj.onc.1210640 | PMID = 17637754 }}</ref>

==Sign out==
===Prostatectomy specimens===
*A prostatectomy that appears to be negative should be worked-up. This is discuss in the ''[[negative prostatectomy]]'' article.
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP checklist].

<pre>
A. LYMPH NODES, RIGHT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

B. LYMPH NODES, LEFT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

C. PROSTATE GLAND AND SEMINAL VESICLES, RADICAL PROSTATECTOMY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4), pT2c pN0.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>

===Transurethral resection of prostate===
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 6/10 (3+3);
-- Approximately 2% of tissue involved;
-- Please see tumour summary.

Comment:
The World Health Organization (WHO) grade is: 1 out of 5.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 7/10 (3+4);
-- Approximately 4% of tissue involved;
-- Please see tumour summary.
- Benign inflamed urothelium.

Comment:
The World Health Organization (WHO) grade is: 2 out of 5. Gleason pattern 3 represents 90% of the tumour, and Gleason pattern 4 represents 10% of the tumour.
</pre>

====Block letters====
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.

TUMOUR SUMMARY - TRANSURETHRAL RESECTION OF PROSTATE (TURP).

PROCEDURE: TRANSURETHRAL PROSTATIC RESECTION.
SPECIMEN SIZE: WEIGHT: 10 GRAMS.
HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).

HISTOLOGIC GRADING:
PRIMARY PATTERN: 3.
SECONDARY PATTERN: 4 (40% OF TUMOUR).
TOTAL GLEASON SCORE: 7 (3+4).

TUMOUR QUANTITATION - PERCENTAGE OF PROSTATIC TISSUE INVOLVED BY TUMOUR: 80 %.

PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
SEMINAL VESICLE INVASION: NOT IDENTIFIED.
LYMPH-VASCULAR INVASION: NOT IDENTIFIED.
PERINEURAL INVASION: NOT IDENTIFIED.

ADDITIONAL PATHOLOGIC FINDINGS:
HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).
NODULAR PROSTATIC HYPERPLASIA.
CHRONIC INFLAMMATION.
</pre>

<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- Adenocarcinoma, Gleason score 7 (3+4)
- Approximately 3% of sampled tissue involved
- Please see tumour summary

Tumour summary:
Procedure: Transurethral resection of prostate
Specimen weight: 11.7 g
Histologic type: Adenocarcinoma, acinar type

Histologic grade:
Primary pattern: 3
Secondary pattern: 4 (<15% of tumor)
Total Gleason score: 7/10 (3+4)

Tumor volume: 3% of tissue

Periprostate fat invasion: Periprostatic fat not identified
Seminal vesicle invasion: Seminal vesicle not identified
Lymphovascular inasion: Not identified
Perineural invasion: Not identified

Additional findings:
Glandular and stromal hyperplasia
Mild chronic inflammation
</pre>

===Biopsy specimens===
Important elements - a list:<ref name=pmid17213347/>
#Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
#Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
#Number of cores and number involved, e.g. "2/3 cores involved by cancer".
#Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour". ‡
#Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
#Presence of [[perineural invasion]].
#Presence of extension into fat (extraprostatic extension).

Notes:
*‡ "Percent area involved" may seem like an odd thing to request 'cause it is sampling dependent, i.e. if the radiologist sticks the biopsy needle deeper into the lesion more of the core is positive, but urologists think it is important -- more important than perineural invasion.<ref name=pmid15223967>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.<ref name=pmid22688447>{{Cite journal | last1 = Fu | first1 = Q. | last2 = Moul | first2 = JW. | last3 = Bañez | first3 = LL. | last4 = Sun | first4 = L. | last5 = Mouraviev | first5 = V. | last6 = Xie | first6 = D. | last7 = Polascik | first7 = TJ. | title = Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer. | journal = Med Oncol | volume = 29 | issue = 5 | pages = 3339-44 | month = Dec | year = 2012 | doi = 10.1007/s12032-012-0270-4 | PMID = 22688447 }}</ref>

====Completely negative====
<pre>
A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

C. PROSTATE, RIGHT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

D. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

E. PROSTATE, RIGHT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

I. PROSTATE, LEFT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

J. PROSTATE, LEFT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

K. PROSTATE, LEFT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
</pre>

====Negative biopsy in surveillance====
<pre>
COMMENT:
The previous results are noted. The absence of cancer in this biopsy may
be due to sampling.
</pre>

====No glands====
<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN FIBROMUSCULAR TISSUE;
- NO PROSTATIC GLANDULAR TISSUE PRESENT.
</pre>

====Inflammation====
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- ACUTE AND CHRONIC INFLAMMATION.
</pre>

====Positive====
<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 25% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

=====Tumour summaries=====
*These are not completely without controversy.
*It should be noted that treatment is driven by the highest Gleason score.{{fact}}

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- TOTAL GLEASON SCORE: 7.
- PRIMARY PATTERN: 4.
- SECONDARY PATTERN: 3.
- PERCENT OF TUMOUR WITH PATTERN HIGHER THAN GRADE 3: 75%.

- NUMBER OF CORES POSITIVE: 10.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 152 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 44%.

- PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: SEMINAL VESICLE NOT IDENTIFIED.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- PERINEURAL INVASION: PRESENT.

- ADDITIONAL FINDINGS: HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA, CHRONIC INFLAMMATION (FOCAL).
</pre>

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- HIGHEST GLEASON SCORE: 8 (4+4).
- SUMMARY GLEASON SCORE: 7 (4+3).
- PERCENT OF TUMOUR WITH PATTERN 4: 55%.
- PERCENT OF TUMOUR WITH PATTERN 5: 0%.

- NUMBER OF CORES POSITIVE: 12.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 178 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 80%.

- PERINEURAL INVASION: PRESENT.
- PERIPROSTATIC FAT INVASION: PRESENT.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: NOT IDENTIFIED.
</pre>

===Seminal vesicle/ejaculatory duct invasion on biopsy===
<pre>
COMMENT:
The seminal vesicles and ejaculatory ducts have the same histology; thus, it is not
usually possible to confidently differentiate them in a needle biopsy.

SV/ED invasion was demonstrated with CK7, CK34betaE12/AMACR, PSA and p63 immunostaining.
The tumour is PSA and AMACR positive.
</pre>

=Intraductal spread of prostate cancer=
==Intraductal carcinoma of the prostate==
*[[AKA]] ''[[intraductal carcinoma]]''.
*[[AKA]] ''intraductal prostate carcinoma''.
{{Main|Intraductal carcinoma of the prostate}}

=Unusual forms of prostate cancer=
==Prostatic ductal adenocarcinoma==
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
{{Main|Ductal adenocarcinoma of the prostate gland}}

==PIN-like prostatic ductal adenocarcinoma==
{{Main|High-grade prostatic intraepithelial neoplasia-like ductal adenocarcinoma of the prostate}}

==Foamy gland carcinoma==
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862>{{Cite journal | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
{{Main|Foamy gland carcinoma}}

==Atrophic prostate carcinoma==
*[[AKA]] ''atrophic carcinoma''.
{{Main|Atrophic prostate carcinoma}}

==Mucinous prostate carcinoma==
{{Main|Mucinous adenocarcinoma of the prostate}}

==Pseudohyperplastic prostatic adenocarcinoma==
*[[AKA]] ''pseudohyperplastic adenocarcinoma''.
{{Main|Pseudohyperplastic prostatic adenocarcinoma}}

==Prostatic signet ring cell carcinoma==
{{Main|Signet ring cell carcinoma}}
===General===
*Very rare - 9 cases in a series of 29,783 prostate cancer cases.<ref name=pmid21123640>{{Cite journal | last1 = Warner | first1 = JN. | last2 = Nakamura | first2 = LY. | last3 = Pacelli | first3 = A. | last4 = Humphreys | first4 = MR. | last5 = Castle | first5 = EP. | title = Primary signet ring cell carcinoma of the prostate. | journal = Mayo Clin Proc | volume = 85 | issue = 12 | pages = 1130-6 | month = Dec | year = 2010 | doi = 10.4065/mcp.2010.0463 | PMID = 21123640 }}</ref>
*Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.<ref name=pmid21123640/>

===Microscopic===
Features:
*Signet ring cells - see ''[[basics]]'' article.

DDx:
*Acinar adenocarcinoma - Gleason pattern 4 with very small glands.

====Images====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRCC (nih.gov)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f7.html#figure-title Prostatic SRCC (nature.com)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f8.html Prostatic SRCC (nature.com)].
*[http://www.webpathology.com/image.asp?case=23&n=34 Prostatic SRCC (webpathology.com)] - looks like ''acinar adenocarcinoma''.

===Stains===
*Alcian blue-PAS stain +ve.
*[[PAS stain|PAS]] -- 50% of cases +ve.<ref name=pmid21123640/>
*[[Alcian blue stain|Alcian blue]] -- 44% of cases +ve.<ref name=pmid21123640/>

==Sarcomatoid carcinoma of the prostate==
{{Main|Sarcomatoid carcinoma of the prostate}}

==Small cell carcinoma of the prostate gland==
{{Main|Small cell carcinoma of the prostate gland}}

==Adenoid cystic/basal cell carcinoma of the prostate==
*Abbreviated ''ACBCC''.
{{Main|Adenoid cystic/basal cell carcinoma of the prostate}}

==Postradiation prostate cancer==
{{Main|Postradiation prostate cancer}}

=Metastatic disease and other cancers of the prostate=
==Urothelial carcinoma==
{{Main|Urothelial carcinoma of the urethra}}

=See also=
*[[Prostate gland]].
*[[Genitourinary pathology]]

=References=
{{Reflist|2}}

[[Category:Genitourinary pathology]]
[[Category:Prostate carcinoma]]

Prostate cancer

2020-03-05T15:36:42Z

Sarah A: /* Prostatic adenocarcinoma variants that mimic benign */

{{ Infobox diagnosis
| Name = Prostate carcinoma
| Image = Prostate cancer with Gleason pattern 4 low mag.jpg
| Width =
| Caption = Prostate carcinoma. [[H&E stain]].
| Micro = major criteria: abnormal architecture (increased gland density, usu. small circular glands, "infiltrative growth" pattern), basal cells lost, cytological abnormalities (nuclear enlargement, nucleoli); minor criteria: nuclear hyperchromasia, wispy blue mucin, pink amorphous secretions, intraluminal crystalloid, amphophilic cytoplasm, adjacent [[HGPIN]], mitoses
| Subtypes =
| LMDDx = [[high-grade prostatic intraepithelial neoplasia]], [[atypical small acinar proliferation]] (biopsy only), [[prostatic atrophy]], [[seminal vesicle]], [[basal cell hyperplasia of the prostate|basal cell hyperplasia]], others
| Stains =
| IHC = PSA +ve, PSAP +ve, AMACR +ve, p63 -ve, CK34betaE12 -ve
| EM =
| Molecular = +/-[[BRCA1]] mutation (genetic predisposition), +/-[[BRCA2]] mutation (genetic predisposition)
| IF =
| Gross = usu. posterior aspect of the prostate - often not apparent at gross
| Grossing = [[prostate biopsy]], [[prostate chips]], [[radical prostatectomy]]
| Staging = [[prostate cancer staging]]
| Site = [[prostate gland]]
| Assdx =
| Syndromes =
| Clinicalhx =
| Signs = firm, nodular prostate on digital rectal exam
| Symptoms = often asymptomatic
| Prevalence = very common
| Bloodwork = PSA elevated (common)
| Rads = hypoechoic areas, no apparent abnormality
| Endoscopy =
| Prognosis = good-to-poor (depends on [[prostate cancer grading|grade (Gleason score)]] and [[stage]])
| Other =
| ClinDDx = [[prostatitis]], [[nodular hyperplasia of the prostate]]
| Tx = observation (common for low-grade, low tumour burden), radiation or radical prostatectomy
}}
This article deals with '''prostate [[cancer]]'''.

The vast majority of prostate cancers are carcinomas and could be labelled '''prostatic carcinoma'''. Most prostatic carcinomas are gland forming; thus, they can be labelled '''prostatic [[adenocarcinoma]]''' or '''adenocarcinoma of the prostate'''.

Benign pathology of the prostate gland, and prostate histology and anatomy are dealt with in the ''[[prostate gland]]'' article.

=Conventional prostate cancer=
==General==
*Very common.
*Increasing incidence with age - the age in years is an approximation of the percentage of men with prostate cancer.<ref>{{cite journal |author=Sakr WA, Haas GP, Cassin BF, Pontes JE, Crissman JD |title=The frequency of carcinoma and intraepithelial neoplasia of the prostate in young male patients |journal=J. Urol. |volume=150 |issue=2 Pt 1 |pages=379–85 |year=1993 |month=August |pmid=8326560 |doi= |url=}}</ref>{{fact}}
*Usually an indolent course - most old men die with prostate cancer ''not'' from prostate cancer.

*Risk increased with a [[BRCA1]] or [[BRCA2]] mutation<ref name=pmid23747895>{{Cite journal | last1 = Li | first1 = D. | last2 = Kumaraswamy | first2 = E. | last3 = Harlan-Williams | first3 = LM. | last4 = Jensen | first4 = RA. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Front Biosci (Landmark Ed) | volume = 18 | issue = | pages = 1445-59 | month = | year = 2013 | doi = | PMID = 23747895 }}</ref> - families have a mix of [[breast cancer]] and prostate cancer.
**BRCA2 mutation risk >8x for men over 65 years old.<ref name=pmid22522501>{{Cite journal | last1 = Castro | first1 = E. | last2 = Eeles | first2 = R. | title = The role of BRCA1 and BRCA2 in prostate cancer. | journal = Asian J Androl | volume = 14 | issue = 3 | pages = 409-14 | month = May | year = 2012 | doi = 10.1038/aja.2011.150 | PMID = 22522501 }}</ref>
**A BRCA2 founder mutation is described in French Canadians.<Ref name=pmid23318356>{{Cite journal | last1 = Taherian | first1 = N. | last2 = Hamel | first2 = N. | last3 = Bégin | first3 = LR. | last4 = Bismar | first4 = TA. | last5 = Goldgar | first5 = DE. | last6 = Feng | first6 = BJ. | last7 = Foulkes | first7 = WD. | title = Familial prostate cancer: the damage done and lessons learnt. | journal = Nat Rev Urol | volume = 10 | issue = 2 | pages = 116-22 | month = Feb | year = 2013 | doi = 10.1038/nrurol.2012.257 | PMID = 23318356 }}</ref>

===Management===
====Dirty first approximation====
*The management changes between [[Gleason score]] 6, 7 (3+4), 7 (4+3) and 8.

Typically, the implications are:
* Gleason 6: observation ''or'' radioactive seeds; surgery if patient wants.
* Gleason 7 with a bit of Gleason pattern 4 and a low tumour volume: it is reasonable to watch ''or'' do something. ‡
* Gleason 7 with a lot of Gleason pattern 4 ''or'' a high tumour volume: do something -- surgery ''or'' radiation therapy.
* Gleason 8+: bad cancer -- do something quickly!

Note:
* ‡ It has been said that ''Gleason score 7 with a bit of Gleason pattern 4 is the new Gleason score 6''.

Bottom line:
*You want to be sure when you call something Gleason pattern 4.

====Observational strategies====
*Delay of definitive treatment (surgery ''or'' radiation).
*Common in the management of prostate cancer.

Classification:<ref name=pmid23126653>{{Cite journal | last1 = Ip | first1 = S. | last2 = Dahabreh | first2 = IJ. | last3 = Chung | first3 = M. | last4 = Yu | first4 = WW. | last5 = Balk | first5 = EM. | last6 = Iovin | first6 = RC. | last7 = Mathew | first7 = P. | last8 = Luongo | first8 = T. | last9 = Dvorak | first9 = T. | title = An evidence review of active surveillance in men with localized prostate cancer. | journal = Evid Rep Technol Assess (Full Rep) | volume = | issue = 204 | pages = 1-341 | month = Dec | year = 2011 | doi = | PMID = 23126653 | url = http://www.ncbi.nlm.nih.gov/books/NBK83054/ }}</ref>
*Active surveillance (AS).
**Low risk of progression.
**May get definitive treatment later.
*Watchful waiting (WW).
**Higher risk of progression.

Note:
*There is no agreed upon set of criteria for active surveillance, and the large number of criteria out there vary significantly.<ref name=pmid22314081>{{Cite journal | last1 = Palisaar | first1 = JR. | last2 = Noldus | first2 = J. | last3 = Löppenberg | first3 = B. | last4 = von Bodman | first4 = C. | last5 = Sommerer | first5 = F. | last6 = Eggert | first6 = T. | title = Comprehensive report on prostate cancer misclassification by 16 currently used low-risk and active surveillance criteria. | journal = BJU Int | volume = 110 | issue = 6 Pt B | pages = E172-81 | month = Sep | year = 2012 | doi = 10.1111/j.1464-410X.2012.10935.x | PMID = 22314081 }}</ref>

=====Active surveillance=====
The ''Klotz'' criteria for active surveillance - pathologic factors only:<ref name=pmid22314081/><ref>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for prostate cancer: for whom? | journal = J Clin Oncol | volume = 23 | issue = 32 | pages = 8165-9 | month = Nov | year = 2005 | doi = 10.1200/JCO.2005.03.3134 | PMID = 16278468 }}</ref>
*Gleason score 6 or less.
*All biopsies cores < 50% involvement.
*One or two cores involved.<ref>URL: [http://www.active-surveillance.com/laurence-klotz-md/ http://www.active-surveillance.com/laurence-klotz-md/]. Accessed on: 12 July 2013.</ref><ref name=pmid23548978>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance: patient selection. | journal = Curr Opin Urol | volume = 23 | issue = 3 | pages = 239-44 | month = May | year = 2013 | doi = 10.1097/MOU.0b013e32835f8f6b | PMID = 23548978 }}</ref><ref name=pmid22891078>{{Cite journal | last1 = Klotz | first1 = L. | title = Active surveillance for low-risk prostate cancer. | journal = F1000 Med Rep | volume = 4 | issue = | pages = 16 | month = | year = 2012 | doi = 10.3410/M4-16 | PMID = 22891078 | PMC = 3412317 }}</ref>
Clinical criteria:
*PSA <= 10 ng/mL.<ref name=pmid22314081/>
*Negative DRE.

==Gross==
*Prostate cancer is uncommonly apparent on gross.
*Classic location: posterior aspect of the prostate.

===Radiology===
*Hypoechoic areas = suspicious for cancer.
**It seems that size of the area matters.
***Small hypoechoic areas (<0.2 cm3) have cancer less than 4% of the time.<ref name=pmid9933054>{{Cite journal | last1 = Fleshner | first1 = NE. | last2 = O'Sullivan | first2 = M. | last3 = Premdass | first3 = C. | last4 = Fair | first4 = WR. | title = Clinical significance of small (less than 0.2 cm3) hypoechoic lesions in men with normal digital rectal examinations and prostate-specific antigen levels less than 10 ng/mL. | journal = Urology | volume = 53 | issue = 2 | pages = 356-8 | month = Feb | year = 1999 | doi = | PMID = 9933054 }}</ref>
***One study suggests hypoechoic lesions tend to have a worse outcome;<ref name=pmid22920545>{{Cite journal | last1 = Nakano Junqueira | first1 = VC. | last2 = Zogbi | first2 = O. | last3 = Cologna | first3 = A. | last4 = Dos Reis | first4 = RB. | last5 = Tucci | first5 = S. | last6 = Reis | first6 = LO. | last7 = Westphalen | first7 = AC. | last8 = Muglia | first8 = VF. | title = Is a visible (hypoechoic) lesion at biopsy an independent predictor of prostate cancer outcome? | journal = Ultrasound Med Biol | volume = 38 | issue = 10 | pages = 1689-94 | month = Oct | year = 2012 | doi = 10.1016/j.ultrasmedbio.2012.06.006 | PMID = 22920545 }}</ref> however, this is not supported by an older study.<ref name=pmid1688955>{{Cite journal | last1 = Devonec | first1 = M. | last2 = Fendler | first2 = JP. | last3 = Monsallier | first3 = M. | last4 = Mouriquand | first4 = P. | last5 = Maquet | first5 = JH. | last6 = Mestas | first6 = JL. | last7 = Dutrieux-Berger | first7 = N. | last8 = Perrin | first8 = P. | title = The significance of the prostatic hypoechoic area: results in 226 ultrasonically guided prostatic biopsies. | journal = J Urol | volume = 143 | issue = 2 | pages = 316-9 | month = Feb | year = 1990 | doi = | PMID = 1688955 }}</ref>

===Prostatectomy grossing===
{{Main|Radical prostatectomy}}

===Cytoprostatectomy grossing===
{{Main|Cystoprostatectomy grossing}}
*Limited sampling of the prostate may lead to undersampling error.<ref name=pmid11182038>{{Cite journal | last1 = Cindolo | first1 = L. | last2 = Benincasa | first2 = G. | last3 = Autorino | first3 = R. | last4 = Domizio | first4 = S. | last5 = De Rosa | first5 = G. | last6 = Testa | first6 = G. | last7 = D'Armiento | first7 = M. | last8 = Altieri | first8 = V. | title = Prevalence of silent prostatic adenocarcinoma in 165 patients undergone cystoprostatectomy: a retrospective study. | journal = Oncol Rep | volume = 8 | issue = 2 | pages = 269-71 | month = | year = | doi = | PMID = 11182038 }}</ref>

==Microscopic==
===Criteria as a list===
Major criteria (the ABCs of prostate pathology):<ref name=pmid17213347>{{cite journal |author=Humphrey PA |title=Diagnosis of adenocarcinoma in prostate needle biopsy tissue |journal=J. Clin. Pathol. |volume=60 |issue=1 |pages=35–42 |year=2007 |month=January |pmid=17213347 |pmc=1860598 |doi=10.1136/jcp.2005.036442 |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860598/?tool=pubmed}}</ref>
#Architecture.
#*Increased gland density.
#*Small circular glands.
#**In rare subtypes - large branching glands.
#*"Infiltrative growth" pattern - malignant glands between benign ones.
#**Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f1.html#figure-title Infiltrative growth pattern (nature.com)].
#Basal cells lacking.
#Cytological abnormalities:
#*Nuclear enlargement (subtle).
#*[[Nucleoli]] (prominent).

Minor criteria:<ref name=pmid17213347/>
#Nuclear hyperchromasia.
#Wispy blue mucin.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f3.html#figure-title Wispy blue mucin (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Pink amorphous secretions.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f11.html Pink amorphous secretions (nature.com)] - from Epstein.<ref name=pmid14739905>{{cite journal |author=Epstein JI |title=Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy |journal=Mod. Pathol. |volume=17 |issue=3 |pages=307–15 |year=2004 |month=March |pmid=14739905 |doi=10.1038/modpathol.3800050 |url=http://www.nature.com/modpathol/journal/v17/n3/full/3800050a.html}}</ref>
#Intraluminal crystalloid.
#*Image: [http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800050f4.html#figure-title Intraluminal crystalloid (nature.com)] - from Epstein.<ref name=pmid14739905/>
#Amphophilic cytoplasm.
#*Amphopilic is said to be ''bluish-red''<ref>URL: [http://pancreaticcancer2000.com/page1.htm http://pancreaticcancer2000.com/page1.htm]. Accessed on: 3 June 2010.</ref> -- though might also be described as ''blue-grey''.
#**Image: [http://www.webpathology.com/image.asp?n=4&Case=20 Amphophilic cytoplasm is prostate carcinoma].
#Adjacent [[HGPIN]].
#Mitoses - quite rare.

Extent/quantity criteria:
*There is no agreed upon minimum number of glands; however, one paper suggests that agreement among experts is low with 5 or less glands.<ref name=pmid20061936>{{Cite journal | last1 = Van der Kwast | first1 = TH. | last2 = Evans | first2 = A. | last3 = Lockwood | first3 = G. | last4 = Tkachuk | first4 = D. | last5 = Bostwick | first5 = DG. | last6 = Epstein | first6 = JI. | last7 = Humphrey | first7 = PA. | last8 = Montironi | first8 = R. | last9 = Van Leenders | first9 = GJ. | title = Variability in diagnostic opinion among pathologists for single small atypical foci in prostate biopsies. | journal = Am J Surg Pathol | volume = 34 | issue = 2 | pages = 169-77 | month = Feb | year = 2010 | doi = 10.1097/PAS.0b013e3181c7997b | PMID = 20061936 }}</ref>
**Thus, it has been suggested that six or more glands should be present to diagnose cancer.<ref name=pmid20061936/>

Features considered pathognomonic for prostate carcinoma by some authorities:<ref name=pmid16613324>{{Cite journal | last1 = Egevad | first1 = L. | last2 = Allsbrook | first2 = WC. | last3 = Epstein | first3 = JI. | title = Current practice of diagnosis and reporting of prostate cancer on needle biopsy among genitourinary pathologists. | journal = Hum Pathol | volume = 37 | issue = 3 | pages = 292-7 | month = Mar | year = 2006 | doi = | PMID = 16613324 }}</ref><ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref>
#Perineural invasion.
#*Must be circumferential (>95% of circumference{{fact}}).
#Glomeruloid bodies.
#[[Collagenous micronodules]] also known as ''mucinous fibroplasia''.

<gallery>
Image: Intraluminal eosinophilic crystalloid of prostate gland - high mag.jpg| Intraluminal eosinophilic crystalloid - high mag. (WC)
Image: Prostate carcinoma with blue mucin -- very high mag.jpg | Whispy blue mucin - very high mag. (WC)
Image: Prostate carcinoma with blue mucin - a1 -- intermed mag.jpg | Whispy blue mucin - intermed. mag. (WC)
</gallery>

===Divided into high and low power===
====Low power features====
*Architecture is the '''key''' to diagnosing low grade cancer.
**Back-to-back glands or crowding of glands -- think low grade cancer (Gleason pattern 3).
**Sharp transition between gland border and lumen.
***Loss of epithelial folding at the epithelium-gland lumen interface - "punched-out" appearance.
**Eosinophilic debris within the gland lumen (pink amorphous secretions, intraluminal crystalloid).
**Blue-tinged acellular material within the gland lumen (mucin) -- uncommon.
**"Infiltrative": small round/oval (malignant) glands (approx. 5 cells across) interspersed with larger (benign) glands that are 2-3 times larger.

====High power features====
*Nuclear changes.
**Hyperchromatic nuclei (like in HGPIN).
**Nuclear enlargement, mild (10%?).
***Difficult to appreciate (if cancer isn't side-by-side with normal prostate).
***Difficult/impossible to see at low power.
*"Large" nucleoli.
**Visible on intermediate and high power (100x / 200x magnification).
***May be difficult to see - especially if light intensity is low or the staining is of poor quality.
***One should not use 400x to look for nucleoli (it is a waste of time + you risk over-calling something benign).
**"Large" is rarely precisely quantified; 3 micrometres has been suggested as "large" based on one study.<ref name=pmid1688728>{{Cite journal | last1 = Kelemen | first1 = PR. | last2 = Buschmann | first2 = RJ. | last3 = Weisz-Carrington | first3 = P. | title = Nucleolar prominence as a diagnostic variable in prostatic carcinoma. | journal = Cancer | volume = 65 | issue = 4 | pages = 1017-20 | month = Feb | year = 1990 | doi = | PMID = 1688728 }}</ref>
***Three micrometres is a little more than 1/3 of [[RBC]] diameter.
*Loss of basal cells - diagnostic feature.
**Like in [[breast pathology]] (where one looks for loss of myoepithelial cells) - this may be difficult to see.

Notes:
*Mitoses are not a common feature.
**If you find them the lesion is probably high-grade.
**Generally, it isn't worth looking for them.

===Mimics===
Mimics of prostate adenocarcinoma:<ref>{{Ref TPoSP|100-3}}</ref>
{| class="wikitable sortable"
! Entity
! Key feature
! Detailed microscopic
! Other
! Image
|-
| Adenosis ([[AKA]] ''atypical adenomatous hyperplasia'')
| gradual transition between normal & small gland (NOT two populations)
| many small glands, lack nuclear size variation, basal layer present
| nucleoli may be present; may need to do p63 or 34betaE12 to find basal layer
| [[Image:Adenosis of prostate_--_intermed_mag.jpg|thumb|150px|center| Adenosis of prostate. (WC)]]
|-
| Sclerosing adenosis
| gradual transition between normal & small gland (NOT two populations), fibrosis
| many small glands, lack nuclear size variation, basal layer present
| analogous to [[sclerosing adenosis of the breast]]{{fact}}
| [http://webpathology.com/image.asp?case=21&n=40 Sclerosing adenosis (webpathology.com)]
|-
| [[atrophy of the prostate|Atrophy]]
| sharp angulation of gland
| nuclear hyperchromasia, scant cytoplasm
| may appear right beside non-atrophic tissue
| [[Image:Atrophic_prostatic_glands_--_high_mag.jpg|thumb|150px|center| Prostatic atrophy. (WC)]]
|-
| [[Basal cell hyperplasia of the prostate|Basal cell hyperplasia]]
| two distinct cell populations (in epithelial component)
| abundant epithelial cells; nucleoli in pale ('blue') nuclei of basal cells, glandular cell nuclei darker ('purple')
| vaguely similar to epithelial hyperplasia of usual type (EHUT) in breast
| [[Image:Basal_cell_hyperplasia_of_prostate_-_high_mag.jpg|thumb|150px|center| Prostatic BCH. (WC)]]
|-
| [[Bulbourethral gland]]
| no nuclear atypia
| clear cytoplasm
| apex of prostate
| [[Image:Bulbourethral gland -- very high mag.jpg |thumb|150px|center| Bulbourethral gland. (WC)]]
|-
| [[Seminal vesicles]] / ejaculatory ducts
| lipofuscin (yellow granular material in cytoplasm), smudge cells (smeared appearance + hyperchromatic)
| fern-like arrangement of epithelium (low power), nucleoli, surrounded by muscle, +/- nuclear inclusions
| involvement by cancer changes staging, lipofuscin may be present in prostate, often has marked nuc. size var.; location: usu. base of prostate
| [[Image:Seminal_vesicle_high_mag.jpg |thumb|150px|center|Seminal vesicles. (WC)]]
|-
| [[Radiation effect]]
| marked nuclear size variation
| increased stroma (fibrosis), lack nucleoli ???
| history of Rx; uniform nuc. size with Hx of Rx should raise susp. of [[postradiation prostatic carcinoma|postradiation cancer]]
| [[Image:Prostate_with_radiation_changes_--_high_mag.jpg|thumb|150px|center|Radiation change. (WC)]]
|-
| Prostatitis
| inflammatory cells (lymphocytes, plasma cells, PMNs)
| no nuclear atypia, normal gland arch.
| clinical mimic of cancer (elevated PSA); usu. not a problem for the pathologist
| [[Image:Inflammation_of_prostate.jpg|thumb|150px|center| Prostatic inflammation. (WC)]]
|-
| [[Vasitis nodosa]]
| sperm within ducts, clinical history (usu. post-[[vasectomy]])
| small tubules, nucleoli common, mild atypia, may "invade" vessels, track along nerves
| mimics metastatic prostate carcinoma, IHC stains: PSA-, PSAP-
| [[Image:Vasitis nodosa -11- intermed mag.jpg|thumb|150px|center| VN. (WC)]]
|}
Memory device: '''AAABBRS''' = atrophy, adenosis, adenosis (sclerosing), basal cell hyperplasia, bulbourethral gland, radiation, seminal vesicles.

===Situations where prostate adenocarcinoma may be missed{{cite journal |vauthors=Yang C, Humphrey PA |title=False-Negative Histopathologic Diagnosis of Prostatic Adenocarcinoma |journal=Arch. Pathol. Lab. Med. |volume=144 |issue=3 |pages=326–334 |date=March 2020 |pmid=31729886 |doi=10.5858/arpa.2019-0456-RA |url=}}===
*Tissue artefacts (try levels and/or IHC)
**Crush artefact obscuring architectural or cytologic features
**Thick section
**Aberration in H&E staining obscuring cytologic features
**Freezing artefact
*Minimal adenocarcinoma
*Prostatic adenocarcinoma variants that mimic benign:
**[[Atrophic prostate carcinoma]].
**[[Pseudohyperplastic adenocarcinoma]].
**[[Foamy gland adenocarcinoma]].
**[[PIN-like adenocarcinoma]].
*Single-cell adenocarcinoma
*Treatment effect

===Prostate cancer grading===
{{Main|Prostate cancer grading}}
It covers the ''Gleason grading system'' and the (new) ''prognostic grade groupings''.

===Staging parameters, margins and more===
====Surgical margins====
{{Main|Surgical margins}}
*Positive is ''tumour touching [[ink]]''.† <ref name=pmid22578729>{{Cite journal | last1 = Lu | first1 = J. | last2 = Wirth | first2 = GJ. | last3 = Wu | first3 = S. | last4 = Chen | first4 = J. | last5 = Dahl | first5 = DM. | last6 = Olumi | first6 = AF. | last7 = Young | first7 = RH. | last8 = McDougal | first8 = WS. | last9 = Wu | first9 = CL. | title = A close surgical margin after radical prostatectomy is an independent predictor of recurrence. | journal = J Urol | volume = 188 | issue = 1 | pages = 91-7 | month = Jul | year = 2012 | doi = 10.1016/j.juro.2012.02.2565 | PMID = 22578729 }}</ref>
**"Close" margins (<0.1 mm) have an increased recurrence risk.<ref name=pmid22578729/>

Notes:
*Surgical margin - where the surgeon cut.
**It is possible to have EPE without a positive margin.
**It is possible to have a positive margin without EPE.
* † Epstein says not touching may be enough, as tumour close to the margin is damaged from the surgery.<ref>URL: [http://urology.jhu.edu/newsletter/prostate_cancer410.php http://urology.jhu.edu/newsletter/prostate_cancer410.php]. Accessed on: 26 March 2013.</ref>

=====Rates and implication=====
Positivity rate varies substantially (13-44%):
*Norway: 26% -- strong dependence on surgeon volume (18% high case load vs. 44% low case load).<ref name=pmid22860630>{{Cite journal | last1 = Steinsvik | first1 = EA. | last2 = Axcrona | first2 = K. | last3 = Angelsen | first3 = A. | last4 = Beisland | first4 = C. | last5 = Dahl | first5 = A. | last6 = Eri | first6 = LM. | last7 = Haug | first7 = ES. | last8 = Svindland | first8 = A. | last9 = Fosså | first9 = S. | title = Does a surgeon's annual radical prostatectomy volume predict the risk of positive surgical margins and urinary incontinence at one-year follow-up? - Findings from a prospective national study. | journal = Scand J Urol Nephrol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.3109/00365599.2012.707684 | PMID = 22860630 }}</ref>
*France: 13-17% -- PSA and prostate size predictors of positivity.<ref name=pmid22860572>{{Cite journal | last1 = Koutlidis | first1 = N. | last2 = Mourey | first2 = E. | last3 = Champigneulle | first3 = J. | last4 = Mangin | first4 = P. | last5 = Cormier | first5 = L. | title = Robot-assisted or pure laparoscopic nerve-sparing radical prostatectomy: What is the optimal procedure for the surgical margins? A single center experience. | journal = Int J Urol | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1442-2042.2012.03102.x | PMID = 22860572 }}</ref>

Note:
*Stage and grade (Gleason score) seem to have less impact than surgeons volume on margin positivity rate.<ref name=pmid22860630/>

The impact of positive margins:
*Significant modest negative affect on long-term outcome in node negative cancers (pT2-4 pN0).<ref name=pmid22901983>{{Cite journal | last1 = Mauermann | first1 = J. | last2 = Fradet | first2 = V. | last3 = Lacombe | first3 = L. | last4 = Dujardin | first4 = T. | last5 = Tiguert | first5 = R. | last6 = Tetu | first6 = B. | last7 = Fradet | first7 = Y. | title = The Impact of Solitary and Multiple Positive Surgical Margins on Hard Clinical End Points in 1712 Adjuvant Treatment-Naive pT2-4 N0 Radical Prostatectomy Patients. | journal = Eur Urol | volume = | issue = | pages = | month = Aug | year = 2012 | doi = 10.1016/j.eururo.2012.08.002 | PMID = 22901983 }}</ref>
*Weaker impact than stage and Gleason score.<ref>{{Cite journal | last1 = Chalfin | first1 = HJ. | last2 = Dinizo | first2 = M. | last3 = Trock | first3 = BJ. | last4 = Feng | first4 = Z. | last5 = Partin | first5 = AW. | last6 = Walsh | first6 = PC. | last7 = Humphreys | first7 = E. | last8 = Han | first8 = M. | title = Impact of surgical margin status on prostate-cancer-specific mortality. | journal = BJU Int | volume = | issue = | pages = | month = Jul | year = 2012 | doi = 10.1111/j.1464-410X.2012.11371.x | PMID = 22788795 }}</ref>
*Bladder neck margin positivity may change the T-stage - see below.

=====Bladder neck margin=====
{{Main|Bladder neck invasion}}
:[[AKA]] ''invasion of the bladder neck''.<ref name=pmid19914651/>
*Bladder neck margin positivity typically is '''pT3a'''.<ref name=pmid23225909>{{Cite journal | last1 = Chung | first1 = MS. | last2 = Lee | first2 = SH. | last3 = Lee | first3 = DH. | last4 = Chung | first4 = BH. | title = Evaluation of the 7th American Joint Committee on cancer TNM staging system for prostate cancer in point of classification of bladder neck invasion. | journal = Jpn J Clin Oncol | volume = 43 | issue = 2 | pages = 184-8 | month = Feb | year = 2013 | doi = 10.1093/jjco/hys196 | PMID = 23225909 }}</ref>
*Seen in approximately 1% of prostatectomies.<ref name=pmid19914651>{{Cite journal | last1 = Pierorazio | first1 = PM. | last2 = Epstein | first2 = JI. | last3 = Humphreys | first3 = E. | last4 = Han | first4 = M. | last5 = Walsh | first5 = PC. | last6 = Partin | first6 = AW. | title = The significance of a positive bladder neck margin after radical prostatectomy: the American Joint Committee on Cancer Pathological Stage T4 designation is not warranted. | journal = J Urol | volume = 183 | issue = 1 | pages = 151-7 | month = Jan | year = 2010 | doi = 10.1016/j.juro.2009.08.138 | PMID = 19914651 }}</ref>

====Extraprostatic extension====
:Abbreviated ''EPE''.
{{Main|Prostate cancer staging#Extraprostatic extension}}

====Seminal vesicle invasion====
:Abbreviated ''SVI''.
{{Main|Prostate cancer staging#Seminal vesicle invasion}}

====Perineural invasion====
{{Main|Perineural invasion}}
*''Not'' a staging parameter.
*Seen in approximately 20% of core biopsies.<ref name=pmid16096404>{{Cite journal | last1 = Ali | first1 = TZ. | last2 = Epstein | first2 = JI. | title = Perineural involvement by benign prostatic glands on needle biopsy. | journal = Am J Surg Pathol | volume = 29 | issue = 9 | pages = 1159-63 | month = Sep | year = 2005 | doi = | PMID = 16096404 }}</ref>
*Complete wrapping of a nerve by epithelium is considered pathognomonic for cancer.<ref name=pmid10435561>{{Cite journal | last1 = Baisden | first1 = BL. | last2 = Kahane | first2 = H. | last3 = Epstein | first3 = JI. | title = Perineural invasion, mucinous fibroplasia, and glomerulations: diagnostic features of limited cancer on prostate needle biopsy. | journal = Am J Surg Pathol | volume = 23 | issue = 8 | pages = 918-24 | month = Aug | year = 1999 | doi = | PMID = 10435561 }}</ref><ref name=pmid16096404/>

Note:
*Occasionally, benign glands are found perineural.<ref name=pmid16096404/>
**These should ''not'' completely wrap around the nerve and should be cytologically benign.

==IHC==
===General recommendations===
ISUP consensus statement:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*Should ''not'' be used if cancer is obvious.
*Should ''not'' be used if it isn't going change the clinical management.

===Prostate markers===
*[[PSA]] (prostate specific antigen) +ve.
*[[PSAP]] (prostatic specific acid phosphatase) +ve. †
*P501S +ve. ‡
*[[NKX3.1]] +ve. ‡

Notes:
*† PSAP may be positive in hindgut [[neuroendocrine tumour]]s.<ref name=pmid>{{Cite journal | last1 = Azumi | first1 = N. | last2 = Traweek | first2 = ST. | last3 = Battifora | first3 = H. | title = Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies. | journal = Am J Surg Pathol | volume = 15 | issue = 8 | pages = 785-90 | month = Aug | year = 1991 | doi = | PMID = 1712549 }}</ref>
*‡ P501S and NKX3.1 are considered second line markers.<ref name=pmid25025364/>
*Prostate carcinoma is typically CK7 -ve and CK20 -ve; however, in high [[Gleason score]] cancers focal positivity of these markers can be seen.<ref name=pmid11888088>{{Cite journal | last1 = Goldstein | first1 = NS. | title = Immunophenotypic characterization of 225 prostate adenocarcinomas with intermediate or high Gleason scores. | journal = Am J Clin Pathol | volume = 117 | issue = 3 | pages = 471-7 | month = Mar | year = 2002 | doi = 10.1309/G6PR-Y774-X738-FG2K | PMID = 11888088 }}</ref>
**CK7: >25-50% staining seen in ~5% of cases.
***>50% staining with CK7 is not report.
**CK20: >25-50% staining seen in ~10% of cases.
***>50% staining with CK20 is not reported.

===Benign prostate versus neoplastic prostate===
*AMACR +ve.
*p63 -ve.
*HMWCK (34betaE12) -ve.

Combination immunostains:
*''PIN-4'' -- consists of: CK5 + CK14 + p63 + P504S (AMACR).<ref>URL: [http://biocare.net/wp-content/uploads/225DS.pdf http://biocare.net/wp-content/uploads/225DS.pdf]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/ http://www.antibodies-online.com/antibody/308235/anti-PIN-4+p63+Cytokeratin+HMW+p504S++AMACR/]. Accessed on: 18 October 2011.</ref><ref>URL: [http://www.webpathology.com/image.asp?case=96&n=5 http://www.webpathology.com/image.asp?case=96&n=5]. Accessed on: 18 October 2011.</ref>
**[[AKA]] ''PIN''.
**[[AKA]] ''CAP''.
***Why '''CAP'''?
****A. '''CA'''ncer of the '''P'''rostate.

Other IHC stains:
*AR +ve -- in prostate confined cancer.
**Usually -ve in lymph node +ve disease.<ref name=pmid20878946>{{Cite journal | last1 = Fleischmann | first1 = A. | last2 = Rocha | first2 = C. | last3 = Schobinger | first3 = S. | last4 = Seiler | first4 = R. | last5 = Wiese | first5 = B. | last6 = Thalmann | first6 = GN. | title = Androgen receptors are differentially expressed in Gleason patterns of prostate cancer and down-regulated in matched lymph node metastases. | journal = Prostate | volume = 71 | issue = 5 | pages = 453-60 | month = Apr | year = 2011 | doi = 10.1002/pros.21259 | PMID = 20878946 }}</ref>

Note:
*Bcl-2 marks basal cells in prostate cancer.<ref name=pmid20189848>{{Cite journal | last1 = Boran | first1 = C. | last2 = Kandirali | first2 = E. | last3 = Yilmaz | first3 = F. | last4 = Serin | first4 = E. | last5 = Akyol | first5 = M. | title = Reliability of the 34βE12, keratin 5/6, p63, bcl-2, and AMACR in the diagnosis of prostate carcinoma. | journal = Urol Oncol | volume = 29 | issue = 6 | pages = 614-23 | month = | year = | doi = 10.1016/j.urolonc.2009.11.013 | PMID = 20189848 }}</ref>

====Prostate carcinoma versus urothelial carcinoma====
The ISUP panel recommends:<ref name=pmid25025364>{{cite journal |author=Amin MB, Epstein JI, Ulbright TM, ''et al.'' |title=Best practices recommendations in the application of immunohistochemistry in urologic pathology: report from the international society of urological pathology consensus conference |journal=Am. J. Surg. Pathol. |volume=38 |issue=8 |pages=1017–22 |year=2014 |month=August |pmid=25025364 |doi=10.1097/PAS.0000000000000254 |url=}}</ref>
*PSA +ve (-ve in UCC).
*GATA3 -ve (+ve in UCC).

Another panel - if GATA3 isn't available:
*Prostate: PSA +ve, p63 -ve, HWMCK -ve.
*Urothelial: p63 +ve, HWMCK +ve, PSA -ve.

Notes:
*AMACR not useful; it is positive in ~50% of [[UCC]].<ref name=pmid16315020>{{Cite journal | last1 = Langner | first1 = C. | last2 = Rupar | first2 = G. | last3 = Leibl | first3 = S. | last4 = Hutterer | first4 = G. | last5 = Chromecki | first5 = T. | last6 = Hoefler | first6 = G. | last7 = Rehak | first7 = P. | last8 = Zigeuner | first8 = R. | title = Alpha-methylacyl-CoA racemase (AMACR/P504S) protein expression in urothelial carcinoma of the upper urinary tract correlates with tumour progression. | journal = Virchows Arch | volume = 448 | issue = 3 | pages = 325-30 | month = Mar | year = 2006 | doi = 10.1007/s00428-005-0129-6 | PMID = 16315020 }}</ref>
*CK7 and CK20 are typically negative in prostate carcinoma, and classically positive in urothelial carcinoma.
*CK34betaE12 may be positive in prostate cancer; 43% of cases in one small series of cases with lymph node metastases.<ref name=pmid9024071>{{Cite journal | last1 = Googe | first1 = PB. | last2 = McGinley | first2 = KM. | last3 = Fitzgibbon | first3 = JF. | title = Anticytokeratin antibody 34 beta E12 staining in prostate carcinoma. | journal = Am J Clin Pathol | volume = 107 | issue = 2 | pages = 219-23 | month = Feb | year = 1997 | doi = | PMID = 9024071 }}</ref>

===Rate of utilization===
*Dependent on practise setting.
**One tertiary academic institution uses it on ~ 40% of cases.<ref>{{Cite journal | last1 = Watson | first1 = K. | last2 = Wang | first2 = C. | last3 = Yilmaz | first3 = A. | last4 = Bismar | first4 = TA. | last5 = Trpkov | first5 = K. | title = Use of immunohistochemistry in routine workup of prostate needle biopsies: a tertiary academic institution experience. | journal = Arch Pathol Lab Med | volume = 137 | issue = 4 | pages = 541-5 | month = Apr | year = 2013 | doi = 10.5858/arpa.2012-0145-OA | PMID = 23273390 }}</ref>

==Molecular changes in prostate cancer==
A fusion gene between ''TMPRSS2'' and ''ERG'' is described.<ref name=pmid20478527>{{cite journal | author = Yu J, Yu J, Mani RS, Cao Q, Brenner CJ, Cao X, Wang X, Wu L, Li J, Hu M, Gong Y, Cheng H, Laxman B, Vellaichamy A, Shankar S, Li Y, Dhanasekaran SM, Morey R, Barrette T, Lonigro RJ, Tomlins SA, Varambally S, Qin ZS, Chinnaiyan AM | title = An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression | journal = Cancer Cell | volume = 17 | issue = 5 | pages = 443–54 | year = 2010 | month = May | pmid = 20478527 | pmc = 2874722 | doi = 10.1016/j.ccr.2010.03.018 | url = }}</ref><ref name=omim602060>{{OMIM|602060}}</ref>
*Both genes are on chromosome 21.
*Currently ''not'' used diagnostically.
*Fusion gene seen in approximately 50% of prostate cancer.<ref name=omim602060>{{OMIM|602060}}</ref>
*A subset of ''TMPRSS2-ERG'' known as ''2+Edel'' (seen in ~7% of all prostate cancer cases) predicts poor survival.<ref name=pmid17637754>{{Cite journal | last1 = Attard | first1 = G. | last2 = Clark | first2 = J. | last3 = Ambroisine | first3 = L. | last4 = Fisher | first4 = G. | last5 = Kovacs | first5 = G. | last6 = Flohr | first6 = P. | last7 = Berney | first7 = D. | last8 = Foster | first8 = CS. | last9 = Fletcher | first9 = A. | title = Duplication of the fusion of TMPRSS2 to ERG sequences identifies fatal human prostate cancer. | journal = Oncogene | volume = 27 | issue = 3 | pages = 253-63 | month = Jan | year = 2008 | doi = 10.1038/sj.onc.1210640 | PMID = 17637754 }}</ref>

==Sign out==
===Prostatectomy specimens===
*A prostatectomy that appears to be negative should be worked-up. This is discuss in the ''[[negative prostatectomy]]'' article.
*[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP checklist].

<pre>
A. LYMPH NODES, RIGHT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

B. LYMPH NODES, LEFT PELVIC, EXCISION:
- ONE LYMPH NODE NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 1 ).

C. PROSTATE GLAND AND SEMINAL VESICLES, RADICAL PROSTATECTOMY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4), pT2c pN0.
-- SURGICAL MARGINS NEGATIVE.
-- PLEASE SEE TUMOUR SUMMARY.
</pre>

===Transurethral resection of prostate===
<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 6/10 (3+3);
-- Approximately 2% of tissue involved;
-- Please see tumour summary.

Comment:
The World Health Organization (WHO) grade is: 1 out of 5.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- ADENOCARCINOMA, Gleason score 7/10 (3+4);
-- Approximately 4% of tissue involved;
-- Please see tumour summary.
- Benign inflamed urothelium.

Comment:
The World Health Organization (WHO) grade is: 2 out of 5. Gleason pattern 3 represents 90% of the tumour, and Gleason pattern 4 represents 10% of the tumour.
</pre>

====Block letters====
<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 7/10 (3+4);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.

TUMOUR SUMMARY - TRANSURETHRAL RESECTION OF PROSTATE (TURP).

PROCEDURE: TRANSURETHRAL PROSTATIC RESECTION.
SPECIMEN SIZE: WEIGHT: 10 GRAMS.
HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).

HISTOLOGIC GRADING:
PRIMARY PATTERN: 3.
SECONDARY PATTERN: 4 (40% OF TUMOUR).
TOTAL GLEASON SCORE: 7 (3+4).

TUMOUR QUANTITATION - PERCENTAGE OF PROSTATIC TISSUE INVOLVED BY TUMOUR: 80 %.

PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
SEMINAL VESICLE INVASION: NOT IDENTIFIED.
LYMPH-VASCULAR INVASION: NOT IDENTIFIED.
PERINEURAL INVASION: NOT IDENTIFIED.

ADDITIONAL PATHOLOGIC FINDINGS:
HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA (HGPIN).
NODULAR PROSTATIC HYPERPLASIA.
CHRONIC INFLAMMATION.
</pre>

<pre>
PROSTATE TISSUE, TRANSURETHRAL RESECTION OF THE PROSTATE (TURP):
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- APPROXIMATELY 5% OF TISSUE INVOLVED;
- PLEASE SEE TUMOUR SUMMARY.
</pre>

<pre>
Prostate Tissue, Transurethral Resection of Prostate (TURP):
- Adenocarcinoma, Gleason score 7 (3+4)
- Approximately 3% of sampled tissue involved
- Please see tumour summary

Tumour summary:
Procedure: Transurethral resection of prostate
Specimen weight: 11.7 g
Histologic type: Adenocarcinoma, acinar type

Histologic grade:
Primary pattern: 3
Secondary pattern: 4 (<15% of tumor)
Total Gleason score: 7/10 (3+4)

Tumor volume: 3% of tissue

Periprostate fat invasion: Periprostatic fat not identified
Seminal vesicle invasion: Seminal vesicle not identified
Lymphovascular inasion: Not identified
Perineural invasion: Not identified

Additional findings:
Glandular and stromal hyperplasia
Mild chronic inflammation
</pre>

===Biopsy specimens===
Important elements - a list:<ref name=pmid17213347/>
#Type of cancer, e.g. "prostatic adenocarcinoma, acinar type".
#Gleason score including primary and secondary pattern, e.g. "Gleason score 3+4=7".
#Number of cores and number involved, e.g. "2/3 cores involved by cancer".
#Percent area involved, i.e. how much of the core is cancer, e.g. "75% of specimen is tumour". ‡
#Percent area involved that is Gleason pattern 4 or 5, e.g. "25% of the tumour is Gleason pattern 4 or 5".
#Presence of [[perineural invasion]].
#Presence of extension into fat (extraprostatic extension).

Notes:
*‡ "Percent area involved" may seem like an odd thing to request 'cause it is sampling dependent, i.e. if the radiologist sticks the biopsy needle deeper into the lesion more of the core is positive, but urologists think it is important -- more important than perineural invasion.<ref name=pmid15223967>{{cite journal |author=Rubin MA, Bismar TA, Curtis S, Montie JE |title=Prostate needle biopsy reporting: how are the surgical members of the Society of Urologic Oncology using pathology reports to guide treatment of prostate cancer patients? |journal=Am. J. Surg. Pathol. |volume=28 |issue=7 |pages=946–52 |year=2004 |month=July |pmid=15223967 |doi= |url=}}</ref>
**There is disagreement on how one should measure patchy cancer (cancer when there is interspersed normal). Epstein believes one should include the interspersed benign if the cancer is patchy, as the groupings of tumour likely join out of the plane of section.<ref name=pmid21788055>{{Cite journal | last1 = Epstein | first1 = JI. | title = Prognostic significance of tumor volume in radical prostatectomy and needle biopsy specimens. | journal = J Urol | volume = 186 | issue = 3 | pages = 790-7 | month = Sep | year = 2011 | doi = 10.1016/j.juro.2011.02.2695 | PMID = 21788055 }}</ref>
**A review by Epstein on the topic of tumour volume suggests it does not have predictive value in multivariante analyses.<ref name=pmid21788055/>
**The biopsy tumour volume is a predictor of Gleason score upgrading on prostatectomy.<ref name=pmid22688447>{{Cite journal | last1 = Fu | first1 = Q. | last2 = Moul | first2 = JW. | last3 = Bañez | first3 = LL. | last4 = Sun | first4 = L. | last5 = Mouraviev | first5 = V. | last6 = Xie | first6 = D. | last7 = Polascik | first7 = TJ. | title = Association between percentage of tumor involvement and Gleason score upgrading in low-risk prostate cancer. | journal = Med Oncol | volume = 29 | issue = 5 | pages = 3339-44 | month = Dec | year = 2012 | doi = 10.1007/s12032-012-0270-4 | PMID = 22688447 }}</ref>

====Completely negative====
<pre>
A. PROSTATE, RIGHT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

B. PROSTATE, RIGHT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

C. PROSTATE, RIGHT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

D. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

E. PROSTATE, RIGHT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

I. PROSTATE, LEFT LATERAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

J. PROSTATE, LEFT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE.

K. PROSTATE, LEFT LATERAL INTERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.

L. PROSTATE, LEFT MEDIAL INFERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE.
</pre>

====Negative biopsy in surveillance====
<pre>
COMMENT:
The previous results are noted. The absence of cancer in this biopsy may
be due to sampling.
</pre>

====No glands====
<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN FIBROMUSCULAR TISSUE;
- NO PROSTATIC GLANDULAR TISSUE PRESENT.
</pre>

====Inflammation====
<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- BENIGN PROSTATE TISSUE;
- FOCAL CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- CHRONIC INFLAMMATION.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL MIDZONE, BIOPSY:
- BENIGN PROSTATE TISSUE;
- ACUTE AND CHRONIC INFLAMMATION.
</pre>

====Positive====
<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED.
</pre>

<pre>
F. PROSTATE, RIGHT MEDIAL INFERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 6/10 (3+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 25% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
G. PROSTATE, LEFT LATERAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 7/10 (4+3);
- 1/1 CORE INVOLVED; APPROXIMATELY 5% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED.
</pre>

<pre>
H. PROSTATE, LEFT MEDIAL SUPERIOR, BIOPSY:
- ADENOCARCINOMA, GLEASON SCORE 8/10 (4+4);
- 1/1 CORE INVOLVED; APPROXIMATELY 15% OF TISSUE INVOLVED;
- PERINEURAL INVASION PRESENT.
</pre>

=====Tumour summaries=====
*These are not completely without controversy.
*It should be noted that treatment is driven by the highest Gleason score.{{fact}}

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- TOTAL GLEASON SCORE: 7.
- PRIMARY PATTERN: 4.
- SECONDARY PATTERN: 3.
- PERCENT OF TUMOUR WITH PATTERN HIGHER THAN GRADE 3: 75%.

- NUMBER OF CORES POSITIVE: 10.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 152 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 44%.

- PERIPROSTATIC FAT INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: SEMINAL VESICLE NOT IDENTIFIED.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- PERINEURAL INVASION: PRESENT.

- ADDITIONAL FINDINGS: HIGH-GRADE PROSTATIC INTRAEPITHELIAL NEOPLASIA, CHRONIC INFLAMMATION (FOCAL).
</pre>

<pre>
TUMOUR SUMMARY - PROSTATE CORE BIOPSIES:
- HISTOLOGIC TYPE: ADENOCARCINOMA (ACINAR, NOT OTHERWISE SPECIFIED).
- HIGHEST GLEASON SCORE: 8 (4+4).
- SUMMARY GLEASON SCORE: 7 (4+3).
- PERCENT OF TUMOUR WITH PATTERN 4: 55%.
- PERCENT OF TUMOUR WITH PATTERN 5: 0%.

- NUMBER OF CORES POSITIVE: 12.
- TOTAL NUMBER OF CORES: 12.
- TOTAL LINEAR MILLIMETERS OF NEEDLE CORE TISSUE: 178 MM.
- PERCENT OF NEEDLE CORE TISSUE THAT IS TUMOUR: 80%.

- PERINEURAL INVASION: PRESENT.
- PERIPROSTATIC FAT INVASION: PRESENT.
- LYMPHOVASCULAR INVASION: NOT IDENTIFIED.
- SEMINAL VESICLE INVASION: NOT IDENTIFIED.
</pre>

===Seminal vesicle/ejaculatory duct invasion on biopsy===
<pre>
COMMENT:
The seminal vesicles and ejaculatory ducts have the same histology; thus, it is not
usually possible to confidently differentiate them in a needle biopsy.

SV/ED invasion was demonstrated with CK7, CK34betaE12/AMACR, PSA and p63 immunostaining.
The tumour is PSA and AMACR positive.
</pre>

=Intraductal spread of prostate cancer=
==Intraductal carcinoma of the prostate==
*[[AKA]] ''[[intraductal carcinoma]]''.
*[[AKA]] ''intraductal prostate carcinoma''.
{{Main|Intraductal carcinoma of the prostate}}

=Unusual forms of prostate cancer=
==Prostatic ductal adenocarcinoma==
*[[AKA]] ''ductal adenocarcinoma of the prostate''.
*[[AKA]] ''prostatic adenocarcinoma, large duct type''.
{{Main|Ductal adenocarcinoma of the prostate gland}}

==PIN-like prostatic ductal adenocarcinoma==
{{Main|High-grade prostatic intraepithelial neoplasia-like ductal adenocarcinoma of the prostate}}

==Foamy gland carcinoma==
*[[AKA]] ''foamy gland adenocarcinoma''.<ref name=pmid19033862>{{Cite journal | last1 = Zhao | first1 = J. | last2 = Epstein | first2 = JI. | title = High-grade foamy gland prostatic adenocarcinoma on biopsy or transurethral resection: a morphologic study of 55 cases. | journal = Am J Surg Pathol | volume = 33 | issue = 4 | pages = 583-90 | month = Apr | year = 2009 | doi = 10.1097/PAS.0b013e31818a5c6c | PMID = 19033862 }}</ref>
{{Main|Foamy gland carcinoma}}

==Atrophic prostate carcinoma==
*[[AKA]] ''atrophic carcinoma''.
{{Main|Atrophic prostate carcinoma}}

==Mucinous prostate carcinoma==
{{Main|Mucinous adenocarcinoma of the prostate}}

==Pseudohyperplastic prostatic adenocarcinoma==
*[[AKA]] ''pseudohyperplastic adenocarcinoma''.
{{Main|Pseudohyperplastic prostatic adenocarcinoma}}

==Prostatic signet ring cell carcinoma==
{{Main|Signet ring cell carcinoma}}
===General===
*Very rare - 9 cases in a series of 29,783 prostate cancer cases.<ref name=pmid21123640>{{Cite journal | last1 = Warner | first1 = JN. | last2 = Nakamura | first2 = LY. | last3 = Pacelli | first3 = A. | last4 = Humphreys | first4 = MR. | last5 = Castle | first5 = EP. | title = Primary signet ring cell carcinoma of the prostate. | journal = Mayo Clin Proc | volume = 85 | issue = 12 | pages = 1130-6 | month = Dec | year = 2010 | doi = 10.4065/mcp.2010.0463 | PMID = 21123640 }}</ref>
*Criteria vary - percentage of SRCs required for Dx varies from 20% to 50%.<ref name=pmid21123640/>

===Microscopic===
Features:
*Signet ring cells - see ''[[basics]]'' article.

DDx:
*Acinar adenocarcinoma - Gleason pattern 4 with very small glands.

====Images====
*[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2996149/figure/F1/ Prostatic SRCC (nih.gov)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f7.html#figure-title Prostatic SRCC (nature.com)].
*[http://www.nature.com/modpathol/journal/v17/n3/fig_tab/3800052f8.html Prostatic SRCC (nature.com)].
*[http://www.webpathology.com/image.asp?case=23&n=34 Prostatic SRCC (webpathology.com)] - looks like ''acinar adenocarcinoma''.

===Stains===
*Alcian blue-PAS stain +ve.
*[[PAS stain|PAS]] -- 50% of cases +ve.<ref name=pmid21123640/>
*[[Alcian blue stain|Alcian blue]] -- 44% of cases +ve.<ref name=pmid21123640/>

==Sarcomatoid carcinoma of the prostate==
{{Main|Sarcomatoid carcinoma of the prostate}}

==Small cell carcinoma of the prostate gland==
{{Main|Small cell carcinoma of the prostate gland}}

==Adenoid cystic/basal cell carcinoma of the prostate==
*Abbreviated ''ACBCC''.
{{Main|Adenoid cystic/basal cell carcinoma of the prostate}}

==Postradiation prostate cancer==
{{Main|Postradiation prostate cancer}}

=Metastatic disease and other cancers of the prostate=
==Urothelial carcinoma==
{{Main|Urothelial carcinoma of the urethra}}

=See also=
*[[Prostate gland]].
*[[Genitourinary pathology]]

=References=
{{Reflist|2}}

[[Category:Genitourinary pathology]]
[[Category:Prostate carcinoma]]

User:Sarah A

2020-03-05T14:42:32Z

Sarah A:

User:Sarah A

2020-03-05T14:42:14Z

Sarah A: /* Edits to work on: */

FANCJ

2020-03-05T14:42:01Z

Sarah A: Redirected page to BRIP1

#REDIRECT [[BRIP1]]

BACH1

2020-03-05T14:41:40Z

Sarah A: Redirected page to BRIP1

#REDIRECT [[BRIP1]]

Hereditary breast cancer

2020-03-05T14:39:17Z

Sarah A: /* See also */

This article deals with '''hereditary breast cancer'''.

'''Familial breast cancer''' redirects to this article.

==Syndromes associated with breast cancer==
{| class="wikitable sortable"
! Gene
! Syndrome
! Cancers
! Notes
|-
| BRCA1
| Familial breast and ovarian cancer<ref name=omim113705>{{OMIM|113705}}</ref>
| breast, male breast, ovarian, prostate, pancreas, fallopian tube
| younger individuals vis-à-vis BRCA2
|-
| BRCA2
| Familial breast and ovarian cancer 2<ref name=omim600185>{{OMIM|600185}}</ref>
| breast, male breast, ovarian, prostate, pancreas, stomach, melanoma, gallbladder, bile duct, pharynx
| older individuals vis-à-vis BRCA1
|-
| TP53 (p53)
| [[Li-Fraumeni syndrome]] ([[AKA]] ''SBLA syndrome'')
| [[sarcoma]]s, brain, larynx, lung, leukemia, [[adrenal cortical carcinoma|adrenal]], breast
| often present in childhood
|-
| CHEK2
| [[Li-Fraumeni syndrome]] (variant)
| see ''p53''
| -
|-
| STK11
| [[Peutz-Jeghers syndrome]]
| breast, gastrointestinal, [[Sertoli cell tumour]], [[granulosa cell tumour]], [[SCTAT]]
| characteristic GI [[hamartoma]]s, mucocutaneous pigmentation
|-
| PTEN
| [[Cowden syndrome]]
| breast, thyroid ([[papillary thyroid carcinoma|PTC]]), endometrial, renal, colorectal
| -
|-
| CDH1
| [[Familial diffuse gastric cancer]]<ref name=omim192090>{{OMIM|192090}}</ref>
| [[invasive lobular carcinoma]], gastric [[signet ring cell carcinoma]]
| -
|-
|}

==BRCA1 and BRCA2==
BRCA1 versus BRCA2:<ref name=Ref_PBoD8_1078>{{Ref PBoD8|1078}}</ref>
{| class="wikitable sortable"
! Gene
! Age
! Histology
! Other cancers
|-
| BRCA1
| younger
| worse types, e.g. triple negative breast ca.
| uterine tube
|-
| BRCA2
| older
| sporadic types
| stomach, melanoma, gallbladder, bile duct, pharynx
|}

Types of cancer associated with both BRCA1 and BRCA2 - ''male OPP'':
*'''Male''' breast, '''o'''varian, '''p'''rostate, '''p'''ancreas.

How to remember types of cancer associated with BRCA2 - ''PUM'':
*'''P'''harynx, '''u'''pper GI (stomach, gallbladder, biliary), '''m'''elanoma.

===Management===
*Women get prophylatic bilateral salpingo-oophorectomies and mastectomies.
**The pathology yield in bilateral salpingo-oophorectomies is significant but modest; in series of 26 prophylatic surgeries (BRCA1 22 individuals, BRCA2 4 individuals) there were 2 in situ carcinoma and 2 atypical proliferations.<ref name=pmid14668548>{{Cite journal | last1 = Carcangiu | first1 = ML. | last2 = Radice | first2 = P. | last3 = Manoukian | first3 = S. | last4 = Spatti | first4 = G. | last5 = Gobbo | first5 = M. | last6 = Pensotti | first6 = V. | last7 = Crucianelli | first7 = R. | last8 = Pasini | first8 = B. | title = Atypical epithelial proliferation in fallopian tubes in prophylactic salpingo-oophorectomy specimens from BRCA1 and BRCA2 germline mutation carriers. | journal = Int J Gynecol Pathol | volume = 23 | issue = 1 | pages = 35-40 | month = Jan | year = 2004 | doi = 10.1097/01.pgp.0000101082.35393.84 | PMID = 14668548 }}</ref> All of the pathology was in BRCA1 carriers.
**In prophylatic procedures, the ovaries and tubes, endometrium, and lower uterine segment should all be [[submitted in total]].<ref name=pmid24495259>{{Cite journal | last1 = Downes | first1 = MR. | last2 = Allo | first2 = G. | last3 = McCluggage | first3 = WG. | last4 = Sy | first4 = K. | last5 = Ferguson | first5 = SE. | last6 = Aronson | first6 = M. | last7 = Pollett | first7 = A. | last8 = Gallinger | first8 = S. | last9 = Bilbily | first9 = E. | title = Review of findings in prophylactic gynaecological specimens in Lynch syndrome with literature review and recommendations for grossing. | journal = Histopathology | volume = 65 | issue = 2 | pages = 228-39 | month = Aug | year = 2014 | doi = 10.1111/his.12386 | PMID = 24495259 }}</ref>

===Sign out===
:See ''[[Uterus#BRCA_carrier]]''.

==Other mutations==
*BARD1 mutations.<ref>{{cite journal |author=Ratajska M, Antoszewska E, Piskorz A, ''et al.'' |title=Cancer predisposing BARD1 mutations in breast-ovarian cancer families |journal=Breast Cancer Res. Treat. |volume=131 |issue=1 |pages=89–97 |year=2012 |month=January |pmid=21344236 |doi=10.1007/s10549-011-1403-8 |url=}}</ref>
==See also==
*[[Breast cancer]].
*[[Hereditary diffuse gastric cancer]].
*[[Serous tubal intraepithelial carcinoma]].
*[[BRIP1]]

==References==
{{Reflist|1}}

[[Category:Breast pathology]]

BRCA1 interacting protein C-terminal helicase 1

2020-03-05T14:38:54Z

Sarah A:

BRIP1 (BRCA1-interacting protein C-terminal helicase 1; AKA BACH1, FANCJ) is a tumour suppressor gene that interacts with BRCA1 to help repair double-strand DNA breaks. <ref>URL: [https://www.ncbi.nlm.nih.gov/gene/83990]. Accessed on: 05 March 2020.</ref> <ref>URL: [https://www.ncbi.nlm.nih.gov/books/NBK1401/]. Accessed on: 05 March 2020.</ref> It is a good example of a gene whose mutations cause clinical manifestations that can be dominant or recessive.

==Disease associations==
*Fanconi anemia <ref>URL: [https://www.ncbi.nlm.nih.gov/books/NBK1401/]. Accessed on: 05 March 2020.</ref>
**with biallelic mutations (autosomal recessive manifestation)
*Breast and ovarian cancer<ref>URL: [https://www.ncbi.nlm.nih.gov/books/NBK1401/]. Accessed on: 05 March 2020.</ref>
**With monoallelic mutation (autosomal dominant manifestation)

User:Sarah A

2020-03-05T14:13:09Z

Sarah A: /* Edits to work on: */

BRCA1 interacting protein C-terminal helicase 1

2020-03-05T14:12:54Z

Sarah A: Created page with "BRIP1 (BRCA1-interacting protein C-terminal helicase 1) is a tumour suppressor gene that interacts with BRCA1 to help repair double-strand DNA breaks. <ref>URL: [https://www.n..."

BRIP1 (BRCA1-interacting protein C-terminal helicase 1) is a tumour suppressor gene that interacts with BRCA1 to help repair double-strand DNA breaks. <ref>URL: [https://www.ncbi.nlm.nih.gov/gene/83990]. Accessed on: 05 March 2020.</ref>

Proton pump inhibitor effect

2020-03-02T15:18:42Z

Sarah A: /* Microscopic */

[[Image:Stomach with prominent parietal cells -- very high mag.jpg|thumb|right|250px|Stomach with PPI effect. [[H&E stain]].]]
'''Proton pump inhibitor effect''', abbreviated '''PPI effect''', is a change seen in the parietal cells of the [[stomach]] due to a drug in the proton pump inhibitor class.

Formally, it is '''stomach with proton pump inhibitor effect'''.

==General==
*Due to intake of a proton pump inhibitor (PPI).
**Used to treat [[gastroesophageal reflux disease]].

===Some proton pump inhibitors===
{| class="wikitable sortable"
! Generic name
! Brand name(s)
|-
|Omeprazole
|LOSEC
|-
|Dexlansoprazole
|DEXILANT
|-
|Lansoprazole
|PREVACID
|-
|Esomeprazole
|NEXIUM
|-
|Pantoprazole
|PANTOLOC
|-
|Rabeprazole
|PARIET
|}

==Microscopic==
Features:<ref>{{Cite journal | last1 = Driman | first1 = DK. | last2 = Wright | first2 = C. | last3 = Tougas | first3 = G. | last4 = Riddell | first4 = RH. | title = Omeprazole produces parietal cell hypertrophy and hyperplasia in humans. | journal = Dig Dis Sci | volume = 41 | issue = 10 | pages = 2039-47 | month = Oct | year = 1996 | doi = | PMID = 8888719 }}</ref> <ref>{{Pathologyoutlines| topic/stomachPPI}}</ref>
*Parietal cell enlargement - '''key feature'''.
**Parietal cells typically bulge into the lumen.
*G cell and enterochromaffin cell-like hyperplasia
**Compensatory change due to increased pH in gastric lumen.
*Multiple fundic gland polyps (with PPI use over several months)
**Polyps may regress after PPI is stopped

===Images===
<gallery>
Image: Stomach with prominent parietal cells -- intermed mag.jpg | PPI effect - intermed. mag.
Image: Stomach with prominent parietal cells -- high mag.jpg | PPI effect - high mag.
Image: Stomach with prominent parietal cells -- very high mag.jpg | PPI effect - very high mag.
</gallery>
www:
*[http://www.nature.com/nrgastro/journal/v4/n8/images/ncpgasthep0896-f3.jpg PPI effect (nature.com)].

==Sign out==
*Usually not reported.

==See also==
*[[Stomach]].
*[[Glycogenic acanthosis of the esophagus]].

==References==
{{Reflist|1}}

[[Category:Stomach]]

User:Sarah A

2020-02-29T00:53:35Z

Sarah A: /* Edits to work on: */

User:Sarah A

2020-02-27T15:09:47Z

Sarah A:

==Edits to work on:==
*Pathology resources
**[[pathology books]]
**online resources
***[[Links]] page
***ExpertPath

*Education etc
**the giving of feedback
**study strategies (appropriate for here? Are there things to quote or would this be too close to original research?)
**research in pathology
***quote the paper on doing research in pathology (in my shared drive)
**use of social media (#pathtwitter)

Residency

2020-02-27T14:38:39Z

Sarah A:

This article is a collection of stuffs for '''residency'''.

In the Canadian context, pathology is usually five years. Unimaginatively, these are simply numbered. The first year is ''[[PGY]]-1'', the second ''PGY-2'', the third ''PGY-3'' and so on. Most of a PGY-1 resident's schedule is devoted to rotations in non-pathology specialties, chiefly in internal medicine and surgery. After the PGY-1 year, the rest of the residency is dedicated to developing competence within pathology.

==See also==
*[[Pathology books]] - list of pathology books - some with reviews.
*[[Junior resident]].
*[[Senior resident]].
*[[Fellow]].

==External links==
*[http://www.gomerblog.com/2014/10/pathology-resident/ Resident Makes Up Disease at Tumour Board, Groundbreaking Discovery (gomerblog.com)].

[[Category:Residency]]

User:Sarah A

2020-02-27T14:32:30Z

Sarah A: Created blank page

Pathology links

2020-02-27T14:27:21Z

Sarah A: /* Interesting pathologists */

[[Image:Broad_chain_closeup.jpg|thumb|right|325px|Don't feel chained... here are links to other sites.]]
The following is a collection of '''pathology links'''.

==Histology==
*[http://www.lab.anhb.uwa.edu.au/mb140/ Blue histology (uwa.edu.au)] - a very good site for histology.
*[http://peir.path.uab.edu/wiki/Histologic Pathology Education Instructional Resource - Histologic (path.uab.edu)] - an introduction to histology with good figures.

==Cytology==
*[http://www.cytologystuff.com/ (cytologystuff.com)] - Cytology images, quizzes, and teaching site.
*[http://www.eurocytology.eu/en/course/3/virtualslides (eurocytology.eu)] - Cervical Cytology Virtual Slides.
*[http://www.cytology-iac.org/educational-resources/virtual-slide-library (ctology-iac.org)] Virtual Slide Library - The International Academy of Cytology.

==General - pathology==
*[http://www.pathologyoutlines.com/ Pathology Outlines] - a good general resource if you have a good handle on the basics - though may be frustrating to navigate.
*[http://pathlabmed.typepad.com/ The Daily Sign-Out (pathlabmed.typepad.com)].
*[http://www.pathologystudent.com/ Pathology Student (pathologystudent.com)] - advertisement free pathology information.
*[http://www.pathguy.com/ The Pathology Guy (pathguy.com)].
*[http://www.pathologynotes.com/ Pathology Notes (pathologynotes.com)].
*[http://granuloma.homestead.com/ Atlas of Granulomatous Diseases by Yale Rosen (granuloma.homstead.com)].
*[http://commons.wikimedia.org/wiki/Category:Images_from_Department_of_Pathology,_Calicut_Medical_College Calicut Medical College - Department of Pathology (wikimedia.org)].
*[http://medicalschoolpathology.com/ Medical School Pathology (medicalschoolpathology.com)] - a full pathology course by Dr. John Minarcik.
*[http://pathology911.com/ Pathology 911 (pathology911.com)] - has some nice [http://pathology911.com/pathosnap/ pathology cases].
*[http://drdoubleb.com/checklists/ Tumor Automatized Reporting Systems (drdoubleb.com/checklists/)].

==Molecular pathology of tumours==
*[http://atlasgeneticsoncology.org/ Atlas of Genetics and Cytogenetics in Oncology and Haematology (atlasgeneticsoncology.org)].

==Interesting pathologists==
*[http://web2.airmail.net/uthman/ Ed Uthman (airmail.net)]
*Jerad Gardner
**A dermatopathologist and soft tissue pathologist known for his educational work on both [https://www.youtube.com/user/JeradMGardnerMD/ YouTube] and [https://twitter.com/JMGardnerMD/ Twitter].

==Tests/Quizzes==
*[http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/quizsidx.html Quizzes with images (med.utah.edu)] - nice small set of images.
*[http://path.upmc.edu/cases/ Online case studies (path.upmc.edu)] - a large set of really nice cases with, unfortunately, mostly crappy low resolution images.
*[http://www.pathologypics.com/FlashCards.aspx Flash cards (pathologypics.com)] - a quiz.
*[http://apps.pathology.jhu.edu/sp Cases at Johns Hopkins (jhu.edu)] - recommended.

===Oklahoma===
*[http://moon.ouhsc.edu/kfung/jty1/opaq/Command/PQ-Welcome-M.htm Pathology quizzes (ouhsc.edu)] - a set of quizzes.
*[http://moon.ouhsc.edu/kfung/jty1/CytoLearn/CytoQuiz/CQ-001-M.htm Cytopathology (ouhsc.edu)].

===India===
*[http://www.histopathology-india.net/PathQuiz.htm A series of surgical pathology cases (histopathology-india.net)] - this site unfortunately has low resolution images.
*[http://www.apconquiz.com/ More Indian quizes (apconquiz.com)].

==Autopsy==
*[http://www.le.ac.uk/pa/teach/va/welcome.html The virtual autopsy (le.ac.uk)] - a set of cases with descriptions of the findings where one is challenged to find the cause of death.

==Staining==
*[http://library.med.utah.edu/WebPath/ Internet Pathology Laboratory of Medical Education (med.utah.edu)].
**[http://library.med.utah.edu/WebPath/HISTHTML/MANUALS/MANUALS.html Stains manual] - nice description of stains.

*[http://en.wikipedia.org/wiki/Main_Page Wikipedia (wikipedia.org)].
**[http://en.wikipedia.org/wiki/Wikipedia:WikiProject_Medicine/Pathology_task_force Pathology task force].

==Micrograph - collections==
*[http://pathorama.ch/ Micrographs from Switzerland (pathorama.ch)].
*[http://www.pubcan.org/index.php?type=about PubCan (pubcan.org)] - a site with information about tumours sponsored by the World Health Organization - unfortunately difficult to navigate.
*[http://www.pathpedia.com/Education/eAtlas/Cases.aspx eAltas (pathpedia.com)].
*[http://radiology.uchc.edu/eatlas/ eAtlas of Pathology (radiology.uchc.edu)].
*[http://cnup.uropat.org/ European Network of Uropathology - Canadian page (uropat.org)].
**[http://enup.org/image-archive/ ENUP image archive (enup.org)].
*[http://www.fujita-hu.ac.jp/~tsutsumi/index.html Pathology of Infectious Diseases (fujita-hu.ac.jp)].
*[http://peir.path.uab.edu/library/ PEIR - a collection of images from the University of Alabama (peir.path.uab.edu)].
*[http://www.virtualpathology.leeds.ac.uk/ Virtual Pathology at Leeds (leeds.ac.uk)].
*[http://imagebank.hematology.org/ American Society of Hematology Image Bank (imagebank.hematology.org)].

===Flickr===
*[http://www.flickr.com/photos/euthman/sets/72057594114099781/ Ed Uthmans's "Specimens" (flickr.com)].
*[http://www.flickr.com/photos/jian-hua_qiao_md/sets/?&page=1 Jian-Hua Qiao photo collection (flickr.com)].
*[http://www.flickr.com/photos/dramnani/ Ramnai's photostream (flickr.com)] - presumably [http://www.uro.com/physicians/dharam-m-ramnani-md/ Dharam Ramnani (uro.com)].
*[http://www.flickr.com/photos/lunarcaustic/ Lunar caustic (flickr.com)] - high quality images.

===Virtual slide boxes===
*[http://www.path.uiowa.edu/virtualslidebox/nlm_histology/content_index_db.html U of I (uiowa.edu)].
*[http://www.papsociety.org/atlas/displayimage.php?album=38&pos=4 Papanicolaou society (papsociety.org)].
*[http://www.pathxchange.org/ A large virtual slide collection (pathxchange.org)].
*[http://rosaicollection.org/index.cfm Rosai Collection (rosaicollection.org)].
*[https://eliph.klinikum.uni-heidelberg.de/atlas/ Institute of Pathology Heidelberg (eliph.klinikum.uni-heidelberg.de/atlas)].
*[http://www.virtualpathology.leeds.ac.uk/ Virtual Pathology at the University of Leeds (virtualpathology.leeds.ac.uk)].
*[http://cancer.digitalslidearchive.net/ Cancer Digital Slide Archive /Emory University (http://cancer.digitalslidearchive.net/)].
*[https://digitalpathologyassociation.org/whole-slide-imaging-repository/ DPA's Slide Imaging Repository (digitalpathologyassociation.org/whole-slide-imaging-repository)].
*[http://slidetutor.upmc.edu/ Interactive dermpath slides, University of Pittsburgh (slidetutor.upmc.edu)].

==Associations==
*[http://www.dgp-berlin.de/ Deutschen Gesellschaft für Pathologie].
*[http://cap-acp.org/ Canadian Association of Pathologists (CAP)].
**[https://mypathologist.ca/ mypathologist.ca] - a slick web site that explains pathology in simple terms.
*[http://www.uscap.org/ United States and Canadian Academy of Pathology (USCAP)].
**[http://www.cap.org/apps/cap.portal?_nfpb=true&cntvwrPtlt_actionOverride=/portlets/contentViewer/show&_windowLabel=cntvwrPtlt&cntvwrPtlt{actionForm.contentReference}=committees/cancer/cancer_protocols/protocols_index.html&_pageLabel=cntvwr CAP cancer checklists].
*[http://www.cap.org/apps/cap.portal College of American Pathologists (CAP)].
*[http://www.canp.ca/ Canadian Association of Neuropathologists (canp.ca)].
*[https://www.cytopathology.org/ American Society of Cytopathology (ASC)].
*[https://www.digitalpathologyassociation.org/ Digital Pathology Association (DPA)].
*[http://slap-patologia.org/ Latin American Society of Pathology (SLAP)].
*[http://ampatologia.org/ Mexican Association of Pathologists (AMP)].

==Pathology mailing lists==
*[http://www.mailman.srv.ualberta.ca/mailman/listinfo/patho-l Patho-l (ualberta.ca)] - an international mailing list in existence since 1994.

==Other wikis==
{{Main|Wikis}}

==Other==
*[http://www.sharinginhealth.ca/site/about.html Sharing in Health (sharinginhealth.ca)].
*[http://www.cancerview.ca Cancer view Canada (cancerview.ca)] - a collection of information about cancer care in Canada.

==See also==
*[[Pathology books]].
*[[Basics]].

[[Category:Pathology links]]